In Vivo Personalised Medicine March 2017

In Vivo vol. 35 â?š no. 03

invivo.pharmamedtechbi.com MARCH 2017

pharma intelligence â?š informa

PERSONALIZED MEDICINE Right patient, right drug, right time, right dose, right price

Patient-Centricity

Companion Diagnostics

Data Analytics

Personalized Trials

In Vivo

March 2017

Pharma intelligence |

One Size No Longer Fits All: The Personalized Medicine Trial Landscape DORO SHIN

THE PERSONALIZED MEDICINE ISSUE

Personalized Medicine: A Patient Primer On Best Practice WILLIAM LOONEY Personalized medicine is focused on meeting patients’ needs, but it also has the potential to transform the delivery and financing of health care. In Vivo probes the path toward meeting both goals in an indepth interview with the National Health Council’s Eleanor Perfetto.

Success rates are higher for clinical trials that incorporate selective pharmacogenomics and pharmacogenetics biomarkers, according to data from Informa’s Trialtrove.

Given the challenges of designing and administering trials to secure regulatory approval in areas of unmet medical need, the data provide some basis for optimism in realizing the promise of targeted, personalized therapies that improve health outcomes for individual patients.

Companion Diagnostics: Moving Beyond Oncology JESSICA LEE, RAVI PATEL, DAVID RUCH AND KATYA MAGONOVA Personalized medicine is becoming the hallmark of care in oncology, but its use is also increasing in other therapeutic areas including inflammation, respiratory, infectious diseases and CNS disorders, as scientific understanding of these diseases advances. The expansion of companion diagnostics beyond oncology has impacts on dealmaking, clinical practice and the R&D pipeline.

Flatiron Aims To Accelerate, Personalize Cancer Research Personalized Medicine: An Infographic NANCY DVORIN AND GAYLE REMBOLD FURBERT There were 132 personalized medicines on the market in 2016, compared with just five in 2008. We present some other key numbers in this rapidly growing field.

©2016 Informa Business Information, Inc., an Informa company

PETER CHARLISH Flatiron Health was formed to exploit a previously untapped source of real-world data on the treatment and clinical outcomes of cancer patients. The company is now working with most of the major players in the oncology sector as well as with the FDA to maximize the benefits of such data analytics.

invivo.pharmamedtechbi.com

CONTENTS ❚

STRATEGIC INSIGHTS FOR LIFE SCIENCES DECISION MAKERS

❚ CONTENTS

In Vivo

March 2017

Pharma intelligence |

DEPARTMENTS

0 Personalized Medicine: A Look Back NANCY DVORIN AND GAYLE REMBOLD FURBERT

AROUND THE INDUSTRY Singulex And Qiagen Partner In Personalized Medicine PETER CHARLISH

In Vivo’s Deals Of The Month: February 2017 NANCY DVORIN

ON THE MOVE Significant recent job changes in pharma, medtech and diagnostics REGINA PALESKI

DEAL-MAKING Deals Shaping The Medical Industry, February 2017 THE STRATEGIC TRANSACTIONS TEAM

EXCLUSIVE ONLINE CONTENT invivo.pharmamedtechbi.com

❚ D eals In Depth

January 2017 AMANDA MICKLUS

❚ Device/Diagnostics Quarterly Dealmaking Statistics, Q4 2016 MAUREEN RIORDAN AND AMANDA MICKLUS

❚ C ardio-Neuro Innovator LivaNova Prepares For Challenges Ahead

invivo.pharmamedtechbi.com

ASHLEY YEO

❚ T rump’s Sights Set On Payers And Pharmas, But Medtechs Must Not Be Complacent ASHLEY YEO

❚ From The Editor The phrase “personalized medicine” first appeared in In Vivo in January 2001 in an article entitled “Millennium Predictive’s Outcome.”

In that story we examined Millennium Pharmaceuticals’ deal with Roche Diagnostics to develop prognostics and therapeutics for rheumatoid arthritis. We found it notable that it was the second deal involving delivery of targets to a large diagnostics company (Millennium’s 1999 tie-up with Becton Dickinson was first), but we were more intrigued that NANCY DVORIN Millennium had opted to reabsorb two-thirds of the programs from its Millennium Predictive Medicine subsidiary, setting the stage for the parent company’s “major, web-based personalized medical information play” by the end of 2001.

It didn’t work out.

Since then, our coverage of personalized medicine has kept pace with business developments in this rapidly growing field, culminating in this issue exclusively devoted to the topic. Behind the oft-repeated mantra – right drug, right dose, right patient, right time – lie many complexities.

We explore some of them inside: how to achieve true patient-centricity in personalized medicine, the expansion of companion diagnostics beyond oncology, the role of data analytics in accelerating the development of targeted therapies, and hard evidence that the use of biomarkers does have a positive impact on clinical trial success.

We start with an amuse bouche on page 4, a timeline of In Vivo’s key articles on personalized medicine over the past 16 years.

This is the first of four themed issues that we are planning in 2017. Next up, an in-depth look at Oncology in May, followed by Dealmaking in September and Market Access in November. We’d love to hear your thoughts on what we should cover those months, or other topics you’d like us to address in 2017. Email me at Nancy.Dvorin@Informa.com.

In Vivo: Always Online First Relevant and exclusive online-only content at your fingertips 24/7.

Full access to our 35-year archive.

Access your subscription by visiting: invivo.pharmamedtechbi.com and log in.

Don’t have an online user account?

Quickly and easily create one by clicking on the “Create your account” link at the top of the page.

Contact: clientservices@pharmamedtechbi.com or call: (888) 670-8900 or +1 (908) 748-1221 for additonal information.

/invivo

@invivo

/invivo

invivo.pharmamedtechbi.com

❚ PERSONALIZED MEDICINE: Patient-Centricity

Personalized Medicine: A Patient Primer On Best Practice Personalized medicine is focused on meeting patients’ needs, but it also has the potential to transform the delivery and financing of health care. In Vivo probes the path toward meeting both goals in an in-depth interview with Eleanor Perfetto, senior vice president for strategic initiatives at the National Health Council, the DC-based patient advocacy organization whose members include groups representing 133 million patients nationwide.

BY WILLIAM LOONEY Tracking the patient perspective on personalized medicine is critical to pharma’s success in commercializing new products.

Patient advocacy groups have knowledge, access and expertise to surmount drug development process hurdles.

invivo.pharmamedtechbi.com

Such groups can provide essential third-party validation of clinical outcomes relevant to the real-world standard of care.

As interest grows in evidence-based “value frameworks” to guide actions on drug access and reimbursement, the addition of a broadly distinctive patient point of view will counter reliance on narrow economic criteria as the driver in decision-making.

E

very missive, every map and model, on the evolving landscape of personalized medicine puts the patient at the center. Yet it’s surprising that many patient advocates don’t feel their perspective is adequately captured as this new treatment paradigm matures from a conceptual vision in the medical literature to an institutional reality at the point of care. One word defines what patient groups want from a system that promises the right medicine, for the right person, at the right time. That word is clarity – about the patient role in the way science and regulation are applied to develop new medicines and how commerce intervenes to set their value and access in the marketplace.

The stake for patients in the process around both is self-evident – but will more clarity bring more clout in delivering the health outcomes that patients want most?

Certainly, the science on precision targeting of medicines to address a patient’s unique genetic expression of disease has advanced faster than the institutions responsible for regulating approval, access and the administration of care. The first reliable scientific measure of personalization arrived back in the 1960s, with the introduction of the Kirby-Bauer test on individual patient susceptibility to different antibiotic drugs. Testing with genetic biomarkers emerged later, in the 1990s. Of the 22 novel drugs and biologics approved by the FDA in 2016, two – Clovis Oncology Inc.’s Rubraca (rucaparib) and Roche’s Tecentriq (atezolizumab) for cancers of the ovaries and bladder, respectively – carry mandates for such tests prior to use in patients. Several other approvals, including Sarepta Therapeutics Inc.’s Exondys 51 (eteplirsen) for Duchenne MD and Biogen Inc.’s Spinraza (nusinersen) for spinal muscular atrophy, also rely on a genetic ID of patients most likely to benefit. The FDA approved two additional diagnostic imaging agents designed to establish a specific treatment pathway invivo.pharmamedtechbi.com

in patients with rare neuroendocrine disorders and recurrent prostate cancer.

Nevertheless, the FDA has only recently moved to establish a mechanism for patient input in evaluating potential curative advances from targeted therapies. A series of pilot consultations with patient groups covering some two dozen disease areas led, in 2016, to the creation of a formal FDA Patient Engagement Advisory Committee. For the first time, the “patient interest” emerged as a certified stakeholder in the FDA institutional process. The DC-based National Health Council (NHC), which represents disease advocacy groups with a collective membership of 133 million patients with chronic diseases, is spearheading a coordinated effort to draft a series of draft FDA guidances to structure engagement by patients throughout the drug R&D life cycle. The objective is to encourage more cooperation between patients, industry and the FDA in defining what is most useful and appropriate in advancing timely drug evaluations.

Patient Pain Points Some aspects of the push toward engagement are likely to be challenging for the NHC and other patient groups seeking a more prominent position at the institutional level. One is the growing desire of payers for hard evidence in proving a medicine actually works. Does this negatively impact the authenticity and passion of the individual patient’s subjective experience of disease? Many patient advocates cite the disease experience as the defining characteristic of what it means to be a patient. Will payers and regulators bend to allow use of real-world qualitative measures such as patient reported outcomes (PROs) in clinical trials? While there is movement in this direction at the FDA, payers and the professional medical community remain skeptical of PROs as a benchmark of efficacy and value. Failure to resolve the ambiguity will continue to disincentivize the drug industry from investing additional resources to generate evidence beyond the randomized clinical trial (RCT).

At the same time, are patient groups ready to support what payers desire most in assessing a drug’s value: head-to-head trials against competitor products relying on the same patient population? For most of industry, it’s a bridge still too far to

In Vivo: For the past decade, personalized medicine has been cited as key to a reformed, patient-centered system of health care delivery. As a leading representative of the organized patient community, do you believe that all stakeholders in the system are now on the same page regarding what personalized medicine is and how it must be applied to improve the practice of medicine?

Eleanor Perfetto: We must differentiate between three themes, each of which can be confusing in relation to the others. These are patient-centered care, personalized medicine and precision medicine. Patients do have a clear view of the concept of patient-centered care – it’s when patients are engaged in their care as full partners, with a clear voice in decisions, working toward the goal of an outcome that is meaningful to them. Decisions are not made for the patient, but with the patient, who ©2017 Informa Business Information, Inc., an Informa company

cross. Likewise, patients, payers and the industry face a discussion around the patient interest in having a vector of individual financial burden included when value is assessed on the basis of economic factors like price and cost.

As volume yields to value as the key criterion for determining access for a new drug in the marketplace, detailed, prescriptive frameworks are being developed under the sponsorship of a wide variety of stakeholders, from academia to insurers, professional associations and even industry – PhRMA itself is quietly constructing pilot value frameworks on drugs for rheumatoid arthritis and multiple sclerosis. Again, groups such as NHC contest being left out of the decision matrix and are pushing their own ideas on how value determination can be refocused more toward outcomes that deliver to patients.

Parsing The Value Question But it’s a fine line that has to be drawn between patient engagement and even tacit endorsement of access decisions that might make patient advocates culpable in limiting drug choices for the very patients they represent. The risk is considerable as these frameworks start making tough choices about value, like justifying a high-tier, high-cost formulary listing or even barring access to a new medicine entirely. Peter Bach, MD, director of the Memorial Sloan Kettering Center’s Center for Health Policy Outcomes, cited this dilemma in a March 8 talk at the annual Cancer Progress summit in New York, noting that if organized patient groups want “skin in the access game” it shouldn’t be done by putting individual patients in the position of having to live with the consequences – like forgoing a child’s future college tuition to pay for a medicine that offers one shot at saving a life.

“Acting in this manner would be unconscionable for any organization purporting to represent the patient interest,” he said.

To shed more light on the issues around a patient-centric agenda on personalized medicine, In Vivo spoke recently with Eleanor Perfetto, PhD, senior vice president for strategic initiatives at NHC and professor of pharmaceutical health services at the University of Maryland School of Pharmacy. Her assessment of the prospects for a truly patient-centered system of care? It’s still a work in progress – but it’s progress nonetheless.

sits in the driver’s seat. Personalized and precision medicine are terms that are often seen as interchangeable. We see it this way: precision medicine relates directly to activation of the genetic component in the diagnostic and treatment setting. For example, a new treatment might be found effective in a group of patients with a certain genotype. Personalized medicine combines the best of all worlds, with providers considering the whole patient around what we call the “chronic care trifecta” – the individual patient’s views about his or her illness, goals of treatment and personal circumstances – along with reliance on biomarkers and genetic indicators applied in the administration of drug therapy. In that context, personalized medicine is always patient-centered.

The most important aspect here is the outcome of treatment relates directly to what is important to the patient, including

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Patient-Centricity ❚

❚ PERSONALIZED MEDICINE: Patient-Centricity factors like quality of life, well-being and functional physical and mental capacities. Patients are partners in care, not study subjects. And personalized means personal. It means having a conversation with the provider that directs treatment toward answering the question: what does health mean to me, the patient? What are the results I want to obtain from treatment? The answer does not necessarily relate to the state of the science.

A therapy might be tailored precisely to an individual’s genetic profile but that does not make it the exemplar of personalized medicine. To call it patient-centered, there must be a connection to the patient experience and what the patient desires as the outcome of treatment.

For other stakeholders, there is a similar understanding of how personalized medicine is supposed to work in the practice of medicine. But in our fragmented delivery system, perception is not always in synch with reality. For example, physicians see themselves as prime advocates for the patient, yet are often reluctant to yield their professional autonomy in return for higher levels of patient engagement. Nevertheless, I believe a broad societal consensus on the importance of personalized approaches to treatment is at hand. Science is moving in that direction and so too is the growing emphasis on value in the financing of care. You can’t prioritize value without making the patient – the ultimate consumer of care – central to the process.

To put it more bluntly, does everyone in our complex system of health care understand what you are talking about?

On a basic level, yes. But the messaging around patient-centered, personalized care could be more explicit. The conversation must be broken down into three easily explained concepts: patient centricity in administration of care; patient-focused drug development; and patient engagement in decision-making, at all levels. Once stakeholders commit to a common understanding of what these concepts mean in practice, the institutional agenda around personalized medicine can progress more quickly.

invivo.pharmamedtechbi.com

Is the biopharmaceutical industry actually talking to patients while new compounds are still being tested in the lab and in the design of clinical trials?

Until recently, the industry did little to incorporate the patient view during drug development, especially at the early stages when crucial decisions are made in bringing compounds forward for human trials. Conversation on the benefit-risk calculation focused entirely on the science. Today, the situation has reversed.

Patients are being solicited to provide insights on what aspects of treatment for a condition need to be emphasized. “What is the impact of your disease on quality of life? What are the preferred outcomes you would like from treatment? Or, here are the side effects I would like to avoid.” The input is guiding decisions on trial design that in turn shape the endpoints, indications and labels of an approved drug. This is a big step forward for patients, especially for those who currently have no treatment options.

Genetic research is allowing physicians and patients to have that conversation I alluded to, with the result that the potential for a positive treatment outcome is statistically much higher. It’s taken well over a decade to get to this point, but the important thing is we are looking forward, not backward.

I am concerned that attention to pricing could slow the progress we’ve achieved. If we lose our focus on patient-centered care, innovations that improve actual clinical outcomes will suffer.

– Eleanor Perfetto, PhD

The NHC is particularly excited about the changes at the FDA, where patient-centered drug development has an unstoppable momentum. The 2012 Prescription Drug User Fee Act [PDUFA V] for the first time required the FDA to solicit patient input in the drug development and approval process. The attitude at the time was that the provision to convene a series of “voice of the patient” meetings was a check-the-box exercise; nothing would change. Gradually, however, opinions began to shift and today we can say these encounters have proved their merit to FDA staff.

What’s on the agenda for the PDUFA VI legislation due for enactment by the new Congress later this year? Is there still a missing regulatory component in the patient engagement process?

The current PDUFA VI commitment letter, which at this point is only that and not yet legislated, mandates the FDA to produce patient engagement guidance on an annual basis. Institutionalizing the process is long overdue. Companies need more guidance on issues like how to engage with patients while avoiding conversations that might appear to be inappropriate communication before a drug obtains marketing approval. We have produced an NHC white paper on what we see as the key barriers to patient engagement in drug development and how to resolve them. A key hurdle is the absence of any guard rails around the communication between the patient community, drug developers and the FDA. But we are quickly overcoming that hurdle.

This raises another issue: methodology. It’s important to identify the specific information that patients can and should provide to drug developers to ensure the FDA has what it needs to make a “patient-centric” approval decision. We need a framework that makes the process more consistent. Technology gives us new ways to achieve this without barring creative approaches to what stakeholders can bring to the table. A few weeks ago we released the first in a series of proposed language “mini-guidance” documents covering topics that we recommend be included in a comprehensive FDA guidance on the patient role in drug development. We are using this list to start a coninvivo.pharmamedtechbi.com

versation for the FDA with our members and other stakeholders which we hope will inform the progress of the required PDUFA VI guidance documents.

How does this work feed into the larger political debate initiated by the Trump administration on reducing the FDA regulatory burden on industry and helping to speed the approval of new drugs for patients with few other options?

Are you concerned that patients will suffer if medicines are approved on safety grounds alone, with efficacy established through direct exposure to the marketplace?

Anything that, in the interest of speed, puts patients at risk – we are firmly against that. Most of this is a philosophical debate about whether the FDA is too prescriptive and risk averse in considering treatments that might help patients. There is no specific rule in play to suspend the FDA evaluation of efficacy with the current standard of evidence, so it is hard to respond.

What about the larger context, in insisting the FDA incorporate real-world evidence (RWE) in its NDA review process?

The NHC is very positive about the discussions relative to the 21st Century Cures legislation enacted in December 2016. There had been some discussion that PDUFA VI would address this topic in a similar manner. Our position is RWE is a complement – not a replacement – to the randomized clinical trial study that remains the basis for FDA drug evaluations. If RWE can buttress the evidence FDA collects through traditional means, ease some of the burden in study design and administration, and help move innovation forward, all without impairing patient safety, then the patient community is going to be favorably disposed.

All this new evidence tends to put more attention on patient quality-of-life issues. Is the regulatory and scientific community where it needs to be in relation to this critical metric?

The FDA is not tone deaf on the quality-of-life issue. It has an obligation to be strict on rigorous methodologies around clinical study endpoints – facts, not opinion, rule the day. The issue for them is not whether quality of life is important; instead, the issue is that quality of life is hard to measure. To the patient, it’s balancing all data sources to inform and drive regulators toward the right decision. That’s the job FDA is supposed to do.

It cannot slack off on methodological rigor if it wants to retain the confidence of industry and the public. That said, we should never ignore information relevant to quality of life in actual clinical practice. It cannot be discounted as a guide to decisions just because it didn’t emanate from the standard RCT. What is the current state of the patient community’s relationship with biopharma companies? The state of play – the pluses and pain points?

I see an abundance of enthusiasm in companies about building a more patient-centered approach to drug development.

Much thought is being expended on organizational changes to ensure the patient perspective informs the clinical development plan. Overall, however, I would say companies are still finding their way – change is always difficult. Business cultures are slow to adapt. For decades, the physician was the go-to target ©2017 Informa Business Information, Inc., an Informa company

for drug developers. Scientists and researchers rely heavily on the literature of the laboratory and professional practice. That narrow orientation doesn’t disappear overnight. But the necessary conversations are taking place and most patient organizations will tell you the dialogue with biopharma is improving at a very rapid pace.

The creation of patient advisory and focus groups in many companies has had a positive effect on what researchers thought they knew about the diseases they study. Instead of addressing it from a purely theoretical point of view, discussions with patients offer insightful details on how physical symptoms affect daily life, especially on functional capabilities that usually escape the scrutiny of clinicians. Slowly companies have come around to the view that engaging patients is not just an expenditure that drives up development costs but a test run to guide the direction of everything from the trial protocol to the final market launch plan.

Biopharma’s heightened interest has increased the time and resource demands on patient organizations. Drug developers want patient input, whether it be joining a KOL advisory board or helping in trial subject recruitment. Our groups also collect significant amounts of data, which companies find desirable, such as in building customized patient registries to support their medicines. While the interest is welcome, there is a drawback in that it may deflect from the mission of these groups to serve their own patient population. Patient groups have to find a balance around that.

What about the payer? How would you describe the state of the relationship between patient groups and those who pay the bills for medicines?

By and large, payers have been relatively slow to embrace the concept of patient centricity. There are popular misconceptions to be overcome: patients are emotional and self-involved; they are ignorant about balancing evidence with costs; they want every imaginable benefit or service associated with their condition. The reality is patients tend to be very grounded. If the case is made rationally, patients are eager to act rationally, especially when they are given information and a choice. No patient is interested in bankrupting the economy just to get treated. The problem is that payers do an inadequate job of answering the question that patients value most: what options do I have? Physicians follow the incentive of the payment system and tend to offer a standardized diagnosis and treatment plan without probing what the patient might desire in the long run.

This approach does not allow for a conversation that ranges beyond a single solution.

Not only is this at odds with the abundant evidence now available to inform health decision-making, it ignores the fact that today patients are assuming more of the cost of their care.

Consumer out-of-pocket costs for medicines are rising due to increased deductibles and formulary co-pays in the major commercial plans. Payers have been slow to recognize that patients are also paying customers, with just as much interest in obtaining value for money as other stakeholders in the health care system.

It should also be noted that some payers are trying new programs that focus on patient-centric care. However, once again,

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Patient-Centricity ❚

❚ PERSONALIZED MEDICINE: Patient-Centricity the definition of patient centric isn’t the one we’d like to see, with the patient treated as a partner rather than a recipient.

The “product value proposition” is the driving force behind the debate on managing the cost of biopharmaceuticals, with a growing array of institutional responses underway to help structure a consistent approach to determining the appropriate price for a branded medicine. The American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), Memorial Sloan-Kettering Cancer Center and the Institute for Clinical and Economic Review (ICER) are leaders in this effort. What is NHC doing to shape this important process in a way that benefits patients?

invivo.pharmamedtechbi.com

We are in dialogue with each of these groups. Progress has been made over the past year. The overall response has been positive in recognizing patients should be involved in the preparation of drug value assessments. But the debate is still in flux; we are nowhere near 100% in terms of agreement. At base, when the question is asked “yes, value, but value to whom?” we want the definitive answer to be, “value to the patient.” Not everyone is fully on board with that.

To us, what matters is the breadth and quality of patient engagement with framework sponsors. We are, for example, not for just a survey of a population with the patient as a study subject.

That is confining. Instead, patients want to be full negotiating partners and to have a seat at the table before decisions on value for products are made. The NHC has prepared a “Patient- Centered Value Model Rubric” that sets criteria for patient centricity and engagement in the design and execution of a value framework. (See sidebar, “Drug Value: It’s Personal, Patients Say.”) One of its key points, for example, is that assessment methodologies must be flexible to account for the heterogeneity of the patient population, in which disease affects each individual patient differently over time, throughout the course of treatment, and from initial diagnosis to recovery to long-term survival.

To capture this, the evidence base used for evaluation must allow for more diversity in sources of data. We need to move beyond just the RCT as the sole benchmark of performance because it fares poorly in measuring outcomes like quality of life, which provides significant insight when examined through the prism of the patient.

A third priority is transparency. Everyone should know the constituent elements of each framework, the assumptions that buttress the methodology, and how the model actually works in practice. To a patient, transparency is simple: where did the data come from and how did you apply it in making the decision as to the value of the product? And, most important, how can I apply it to my own situation, with my physician and caregivers?

What success have you had in using the Rubric to shift these frameworks toward a more patient-oriented perspective?

Where are you in the discussions initiated with ICER last September over its latest update to the ICER Value Assessment Framework?

We have a mixed reaction to the update. On the positive side, we are pleased to see a specific commitment from ICER to integrate patients in the evaluation process. The group is open to including more sources of evidence in the review protocols,

including outcomes data that are important to patients. But we’d still like to see more detail on exactly how patient groups will be engaged, especially through actions that ensure the patient voice will be amplified at the earliest stages of a review, not at a later phase when patient input becomes essentially irrelevant.

For example, we continue to believe every ICER assessment should publicly disclose comments submitted by stakeholders, including whether the information was used in the evaluation – or not – and why. Generally, however, the relationship with ICER is positive and progressing. I am confident we will find additional ways to work together going forward.

What are the key remaining barriers to institutionalizing the patient role in value frameworks?

There is a disconnect between what we know is the increased contacts that patients have with these value framework organizations and what is codified in their rules and methodologies. Groups like NHC are helping to do the “matchmaking” between framework developers and the patient community, yet it is still hard to identify the level of engagement when reading the value assessment reports released to the public. The true patient contribution to the process is unknown or unclear in the documents payers and other key stakeholders read when considering what they should pay for a new medicine. Consistency among the frameworks in disclosing patient involvement would help a great deal. We’d like to see that change, and for there to be more transparency.

Is the focus on a generalized approach to value frameworks misplaced? Might it be better to tie this work to the mandates of the professional disease organizations responsible for operationalizing the science around a single condition or therapy area?

This is a complicated issue. It sounds logical to put decisions on value in the hands of those with real expertise in a defined therapeutic area. But in practice, introducing one framework for one condition imposes a daunting hurdle because one disease and one set of treatments is not a viable instrument to address the fact that most patients suffer from multiple co-morbidities.

For an aging population with diabetes, hypertension or congestive heart failure, how do you create a conceptual framework to incorporate such a diversity of conditions and adjust the methodology to fit the circumstances of the individual patient? It’s a bridge too far right now. I believe it will intensify as a problem if or when frameworks become an accepted standard practice in reimbursement and market access.

Is the momentum behind personalized medicine unstoppable? Do you see any potential for backtracking from a patient-centric vision of health care?

This is no passing fad. President Obama’s Precision Medicine Initiative [PMI] was the definitive signal that a personalized approach to medicine had finally achieved critical mass. Focus on the patient is becoming more mainstream every day. Regardless of what happens to the Affordable Care Act [ACA] under the new Trump administration, the defining questions of a reform agenda remain the same: how do we make our health care institutions more responsive to patient needs and views? How do we apply all invivo.pharmamedtechbi.com

❚ DRUG VALUE:

IT’S PERSONAL, PATIENTS SAY

In a series of meetings and workshops over the past 18 months, the National Health Council has developed a platform that consolidates the patient community’s perspective on how to assess value in choosing among alternative therapies in biopharmaceuticals and other key health care interventions. The Patient-Centered Value Model Rubric is being offered to a wide range of stakeholders to shape their actions on value. It will also be used by the NHC in evaluating the merits for patients of those “value frameworks” now being introduced by academic, payer and professional organizations.

The Rubric defines “patient” as consisting of three groups: the individual patient, caregivers and patient organizations.

It takes pains to distinguish the patient from a “consumer” of health care, noting the latter implies a dominant economic or purchasing context, whereas what really defines a patient is someone who has or is at risk for developing a serious medical condition. The text also presents a specific patient approach to value, stating that it is not a fixed concept but can vary over time according to what the patient experiences day to day.

Finally, the Rubric places “personal benefit” at the top of the value chain for patients, stating that value can never be seen as just an economic calculation.

The NHC document concludes with a list of six “domains” of a patient-centered value framework. These are: Partnership – involvement of patients in all steps relating to development and dissemination of a value model, as well as the opportunity to participate in the process once established.

Transparency – full disclosure to the patient community and the public of the assumptions that underlie a working value model as well as the inputs that drive assessment methodologies. Funding sources for the model or the sponsoring organization should be identified and acknowledged publicly.

the new science to target the right treatments for the individual patient? What medical practice policies and procedures will best drive outcomes in line with patient preferences?

It remains to us to debunk the persistent myth that personalized medicine is a cost driver, not a cost saver. We know that when patients are involved and have the best knowledge available about their own condition and options, they make the right choices. In many cases, the right choices are the least expensive.

Many observers of the biopharmaceutical industry note that the targeted therapies encouraged by personalized medicine can be very expensive. Will it become harder for patient organizations to make the case for personalized medicine if drugmakers continue to set high prices for medications designed for a progressively smaller cohort of patients?

Drug companies justify the prices they charge for a new medicine as the consequence of strict regulation and lengthy, high-stake investments in research. Truly egregious instances of pricing tend to come from smaller, renegade players rather than big pharma. Nevertheless, the industry has to do better in ©2017 Informa Business Information, Inc., an Informa company

Inclusiveness – value model sponsors should offer opportunity for comment to all interested stakeholders, including patients. Participation from a medical ethics expert is desirable to maintain open channels to different points of view beyond that of the payer.

Diversity – sponsors need to recognize the diversity of views among the patient population regarding value assessments and to incorporate this diversity in their methodologies. This includes evaluating data around patient subpopulations as well as recognizing how the trajectory of disease varies from patient to patient.

Outcomes – methodologies should identify and track outcomes that patients deem to be important, including day-today functional status, health-related quality of life, well-being, survival, productivity and financial stress. Economic value data should be expanded to include the patient burden in drug costs, such as out-of-pocket outlays for prescriptions.

Data sources – incorporate different but credible forms of data that are patient centered, such as patient-reported outcomes reports, patient registries and real-world evidence.

NHC’s Eleanor Perfetto, PhD, says that an issue that comes up often in discussion with developers of value frameworks is what the patient movement means by the notion of “responsiveness.” The answer, according to Perfetto, is simple: “It’s giving patient representatives a level of consultation and involvement from the time when assumptions about methodology are defined to the ultimate decisions on access.” What counts is procedural clarity, expressed in a format understandable to a patient whose illness may expose them to the consequences – good or bad – of that decision.

IV005052

explaining why some drugs are priced at a stiff premium to the current standard of care. While some higher priced products have been shown to offer greater value to patients than standard of care, for others it is unclear. Greater transparency on pricing and insurance plan design is one way to address this.

I am concerned that attention to pricing could slow the progress we’ve achieved. If we lose our focus on patient-centered care, innovations that improve actual clinical outcomes will suffer. There will be fewer options for patients, particularly those with rare diseases. We should be creating a health care system that drives patients to higher value care and discouraging lower value care. Solving this requires a conversation more honest than what we as a society have conducted to date. And the critique must extend to other health interventions – a larger conversation than targeting a single new drug for scrutiny while other cost drivers in the overall system go untouched. It’s easy to single out one factor. It’s hard to solve the bigger problem. But the onus is on the industry to take more initiative.

IV005050 Comments: Email the author: William.Looney@Informa.com

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Patient-Centricity ❚

❚ PERSONALIZED MEDICINE: Companion Diagnostics

Personalized medicine is becoming the hallmark of care in oncology, but its use is also increasing in other therapeutic areas including inflammation, respiratory, infectious diseases and central nervous system disorders, as scientific understanding of these diseases advances. The expansion of companion diagnostics beyond oncology has impacts on dealmaking, clinical practice and the R&D pipeline.

BY JESSICA LEE, RAVI PATEL, DAVID RUCH AND KATYA MAGONOVA Takeda and AstraZeneca are investigating biomarkers with their latestage assets for Alzheimer’s disease and asthma, respectively, indicating that companion diagnostics have the potential to reach beyond specialty therapeutic and rare disease areas in the near term.

invivo.pharmamedtechbi.com

Multi-biomarker assays are an area of interest among pharmaceutical and diagnostics developers, and clinicians are interested in using them to inform their treatment decisions. inVentiv Health’s survey of practicing oncologists in the US finds that 90% believe multi-biomarker diagnostics will be accepted as the standard of care within the next three to five years.

E

xpanding personalized medicine beyond the oncology sphere offers significant upside, including targeted use in patients most likely to benefit as well as adding value to the health care system. However, there are unique development and commercialization challenges associated with pairing a therapy with a companion diagnostic. Proper preparation and expertise is required to avoid potential pitfalls, such as partnership challenges and education requirements for expanded audiences at launch. Additional considerations for a successful drug-companion diagnostic launch include demonstrating clear value to both providers and payers, both of whom are critical drivers of uptake.

Advancing personalized medicine is becoming the goal of many drug manufacturers, as is evident by the number of such therapies in clinical development. According to the FDA, more than 20% of new molecular entities (NME) approved by the FDA in the last three years – and 27% of the 22 NME approvals in 2016 alone – can be classified as a personalized medicine, not including previously approved therapies. Half of the personalized medicines approved in 2016 (three) were indicated in oncology. The others had indications for either infectious or rare disease. This trend signifies a major shift in the way drug companies are organizing and thinking about commercializing pipeline assets – likely as a way to differentiate therapies in crowded markets (e.g., oncology, hepatitis C) or demonstrate greater value due to their ability to selectively target appropriate patient populations most likely to benefit.

Dealmaking On The Rise Companion diagnostics that can help identify the right patient for the right drug at the right time are playing a major role in this shift toward personalized medicine in areas beyond oncology. An analysis of recent deals in diagnostics shows that companion diagnostics deals, as a percentage of all diagnostics partnerships (including

invivo.pharmamedtechbi.com

Gayle Rembold Furbert

Companion Diagnostics: Moving Beyond Oncology

licensing agreements, asset purchases, joint ventures, etc.), have held relatively steady over the past five years, despite an overall decrease in the number of diagnostics deals.

For example, in January 2016, NanoString Technologies Inc., Medivation Inc. and Astellas Pharma Inc. announced a partnership to develop and commercialize a triple-negative breast cancer (TNBC) companion diagnostic for enzalutamide based on a cancer gene expression signature algorithm from NanoString, in a partnership agreement with a disclosed value of $22 million.

NanoString will modify its existing Prosigna Breast Cancer Assay, a multiplexed biomarker test, as a companion diagnostic for enzalutamide in TNBC, a form of breast cancer with relatively high unmet need.

Beyond oncology, NuSirt Biopharma and OWL Metabolomics forged a partnership to develop a blood-based companion diagnostic for NuSirt’s NS-0200, currently in Phase II trials for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), an increasing cause of liver transplantation. OWL Metabolomics’ approach to development of this companion diagnostic is to analyze a patient’s lipidomic signature over certain time intervals to measure specific markers of histopathological change in the liver.

Currently, liver biopsy is the gold standard in the diagnosis of NASH; OWL’s technology will utilize minimal blood draws (>0.5 ml), offering a significant benefit over surgery and its related potential complications. Development of NASH therapies is expected to address a major unmet need in a disease area with no approved therapies. Driven by a crowded pipeline and historically low success in NASH clinical trials, these companies are seeking to differentiate therapies and improve odds of trial success to ultimately evolve a new standard of personalized care.

Evolving Paradigms As companion diagnostics become more common, the traditional paradigm of “one biomarker, one disease” (such as treating an anaplastic lymphoma kinase [ALK] fusion in non-squamous cell lung cancer [NSCLC] with an ALK inhibitor) is expected to evolve to “multiple biomark-

ers, one disease” or “one biomarker, multiple diseases.” For example, the National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI-MATCH) trial is investigating this with a 24-arm study exploring the potential for treating cancer patients with currently available targeted therapies based on the molecular profiles of their tumors, regardless of a product’s specific indication (e.g., evaluating crizotinib in ALK-mutated breast cancer).

According to William Grady, MD, of the Fred Hutchinson Cancer Research Center and director of translational research at the University of Washington Medical School Gastroenterology Division, “The hope is that we’ll be able to better use targeted therapies by directing them to the molecular target in the cancer rather than by directing their use based on the tissue of origin of the cancer. However, what the NCI-MATCH trials are showing is that in only about 10% of the cases where the cancers have the predicted targets that should cause the cancer to be sensitive to the therapy are we seeing a clinical effect; in 90% of the cases that have the appropriate targets, the cancers are turning out to not be responsive.” He says more work is needed to better understand cellular and molecular pathways in cancer, but there is a high likelihood that a combination treatment approach with multiple targeted therapies will be able to attack the dynamic cellular features that change with time in cancer cells.

Multi-biomarker assays, similar to Foundation Medicine Inc.’s FoundationOne and next-generation sequencing panels, may help to fill the void in current understanding of molecular targets.

Grady continues, “What we’re discovering with functional assays is that some of the targets are completely unexpected, which means new possibilities for using other platforms to predict these targets.

These assays will be another way forward” toward understanding genomic and molecular characteristics of disease through retrospective analyses to match potential drug-molecular target pairs. For example, Ignyta Inc.’s STARTRK-2 trial is incorporating powerful technologies, such as next-generation sequencing and proprietary algorithm-based biomarker panels, to identify and characterize genetic or molecular variation (TrkA, TrkB,

©2017 Informa Business Information, Inc., an Informa company

TrkC, ROS1 and ALK) in cancer patients in combination with an investigational therapeutic, entrectinib.

Ignyta’s unique business model, in which it is developing both the drug and the diagnostic in-house, is enabling the rapid exploration of molecular biomarkers implicated in pan-tumor settings (i.e., NSCLC, colorectal cancer, salivary gland cancer and astrocytoma) in ways that may foreshadow the future of biomarker testing and companion diagnostics development.

Survey Results: Biomarkers’ Emerging Role In Clinical Practice Not only are multi-biomarker assays an area of interest among pharmaceutical and diagnostics developers, clinicians are interested in using these assays to inform their treatment decisions as well.

In a survey conducted by inVentiv Health Consulting with 85 oncologists (n = 30) and non-oncologists (n = 55), an overwhelming majority of oncologists (90%) stated they believed that multi-biomarker diagnostics will be the standard of care within the next three to five years, with 64% of oncologists believing they will be testing at least 60% of their patients with next-generation sequencing to make treatment decisions within the next three to five years. (See Exhibit 1.)

While oncologists reported high rates of familiarity with next-generation sequencing applications, the same was also true for non-oncologists. Among the 55 non-oncologists surveyed (i.e., rheumatologists, pulmonologists, neurologists and PCPs), only 9% reported low or very low familiarity with next-generation sequencing. Non-oncology physicians also anticipated using personalized medicine approaches in regular practice, with 79% expressing high or very high likelihood that they will be using biomarker assays in the future, if available.

An even higher number (85%) indicated that a diagnostic-therapy combination would increase their confidence in using the therapy because of the potential for increased efficacy, the availability of a new treatment option, the potential for greater patient satisfaction and safety, and increased confidence that the right patient will receive the right therapy. (See Exhibit 2.) Two-thirds of all physicians

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Companion Diagnostics ❚

❚ PERSONALIZED MEDICINE: Companion Diagnostics Exhibit 1

Oncologists Say Multi-biomarker Diagnostics Will Become The Standard Of Care

Oncologists

90%

10%

■ Yes ■ No

Q:

Do you envision using multigene/multibiomarker diagnostic assays similar to FoundationOne, Oncotype Dx, Mammaprint, etc. as the standard of care in treatment decision making in the future (3-5 years)?

SOURCE: inVentiv Health

surveyed (including oncologists and nononcologists; n = 85) felt that personalized therapies with an associate companion diagnostic will be available for many conditions outside of oncology within the next five years. This high degree of anticipation and awareness of personalized medicine suggests that adoption of future novel biomarker-driven therapies is primed for rapid uptake. (See sidebar, Survey Points To Biomarkers’ Emerging Role In Clinical Practice.)

invivo.pharmamedtechbi.com

A Diversifying Pipeline Indeed, well-studied therapeutic areas with numerous treatment choices in inflammatory disease (e.g., rheumatoid arthritis, irritable bowel disease) and infectious diseases are likely to be fruitful areas for companion diagnostics development in the near future. This is in addition to those therapeutic areas that already have the attention of biopharmaceutical companies (i.e., Alzheimer’s disease and NASH) due to the absence of approved therapies. Analysis of the current companion diagnostics development pipeline shows that almost half of therapies currently in Phase III are associated with a biomarker diagnostic intended for use outside of oncology. (See Exhibit 3.)

For example, Takeda Pharmaceutical Co. Ltd.’s AD-4833, currently in Phase III for Alzheimer’s disease, is leveraging a growing practice from oncology – that is, testing for multiple biomarkers using a risk assignment algorithm, similar to Prosigna or Genomic Health Inc.’s Oncotype Dx, which can predict the risk of breast

and colon cancer recurrence using multiple genes. These types of assays have found a valuable niche among oncologists due to their ability to effectively help inform and guide treatment decisions for cancer patients, driven by inclusion in National Comprehensive Cancer Network (NCCN) guidelines. In addition to broad physician uptake, payers have supported the use of these assays through ensuring coverage in most commercial plans.

The goal of Takeda’s trial is to evaluate the safety and efficacy of AD-4833 in delaying the onset of mild cognitive impairment due to Alzheimer’s disease and to validate a risk-based biomarker algorithm for determining this, developed in conjunction with pharmacogenomics company Zinfandel Pharmaceuticals Inc. The assay is evaluating three factors: APOE, TOMM40 genotypes and age to produce a risk score for developing early onset Alzheimer’s disease. The disease is an increasing focus for this type of effort due to the large and growing patient population as well as efforts to better understand the underlying pathophysiology that leads to disease progression.

Key Considerations For Success Innovators seeking to successfully launch personalized medicine therapies must give thoughtful consideration to the development and commercialization of the associated companion diagnostic.

This often begins with the selection of the proper diagnostic partner. Careful coordination is required to develop a drug and diagnostic together. Often,

smaller, emerging companies may be the most at risk due to limited resources and knowledge of drug commercialization.

Key considerations in the partnership equation include: • Timing: When should we partner? How should we coordinate and manage the alliance?

• Capabilities: What capabilities should the ideal partner have? Do they have a track record of experience?

• Scale: Does the partner have financial stability/access to capital and have the ability to scale at launch?

It is also important to keep in mind that incentives for the drug developer and diagnostics partner are very different.

Often the primary benefit will go to the drug developer – that is, shortened time to approval and reduced development costs, greater revenues, differentiation as a personalized medicine, etc. Thus, therapeutics companies must carefully consider the investments they may need to make in biomarker strategy and partnership structure.

Early Planning Is Key With early planning and execution, the benefits of partnering with the right diagnostics developer can be tremendous, starting with the opportunity to tailor the drug development program and clinical trial design much earlier in the process.

Choosing a diagnostics partner too late invivo.pharmamedtechbi.com

Exhibit 2

Drivers For Increased Confidence In Using CDx Outside Of Oncology Improved efficacy potential

58%

New treatment options

45%

Patient satisfaction

35%

Improved safety potential

40%

Increased confidence that the right patient will receive the therapy

38%

0%

Q:

20%

40%

60%

80%

100%

What are potential drivers of your decision that may increase your confidence to prescribe a particular drug with an associated biomarker test?

SOURCE: inVentiv Health

Exhibit 3

Companion Diagnostics Pipeline 35

38% 2 2 1 2

# Of Clinical Trials With A CDx

30 25

■ ■ ■ ■ ■ ■

5 20

46% 2 2 2

15 10 5 0

0% 7

20

7

Phase I

Phase II

Phase III

Other Renal Metabolic CV CNS Oncology

= % Non-Oncology SOURCE: inVentiv Health

into clinical development runs the risk that the companion diagnostic assay won’t be developed, validated, and approved by the time of drug approval.

This can lead to potential confusion and inefficiencies during development and launch planning and, most importantly,

poor uptake and failure to realize the full commercial potential of the therapeutic.

Companion diagnostic development and optimization should be completed prior to pivotal trial initiation to increase the likelihood of simultaneous launch. Diagnostics companies may have different

©2017 Informa Business Information, Inc., an Informa company

expectations and it is important for both partners to gain alignment.

With or without a partner, making an early decision to utilize a biomarkerbased strategy may help reduce exposure to the risk of clinical trial failure and subsequently improve return on investment.

In the largest study of clinical drug development success rates to date (more than 9,500 phase transitions), a BIO Industry Analysis using data from Informa’s Pharma Intelligence’s Biomedtracker found that between 2006 and 2015, therapies that utilized biomarkers as inclusion or exclusion criteria had a three-fold higher likelihood of approval (25.9% from Phase I to approval) compared with drugs that do not have an associated selection biomarker (8.4%).

At launch, the adoption of personalized medicine is heavily dependent on stakeholder education, and detailed launch planning is key to preparing the market. Generally, launches with companion diagnostics include more customer stakeholders than the traditional drug launch. In addition to the traditional stakeholders (e.g., prescribers, nurses and payers, etc.), education of appropriate lab personnel is also required to ensure awareness of the companion diagnostic and help guarantee uptake of the novel therapy. This may require development of additional marketing materials or even coordination of sales teams to incorporate a laboratory call point.

Communication And Trust Drive Success Nothing is more important to a successful companion diagnostics partnership than excellent communication from start to finish – a key factor in which is trust.

Trust can be built or frayed around such issues as intellectual property sharing, the timing and strategy surrounding market development and educational initiatives, progress updates and the like.

Even differences in corporate culture can make it difficult for partners to communicate with each other effectively.

To mitigate these risks, it is vital to establish a regulatory communication plan at the outset. Partners should communicate with each other before and after each FDA interaction. Both drug

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Companion Diagnostics ❚

❚ PERSONALIZED MEDICINE: Companion Diagnostics and companion diagnostics partners should consider and align on marketing strategies for pathology labs that will be involved in terms of investment, messaging, education, training and marketing materials. During the launch window, communication between the partners needs to continue to ensure optimal uptake.

As we’ve seen, personalized medicine is anticipated to continue changing treatment paradigms and evolve beyond oncology with the aid of companion diagnostics. A successful drug-companion diagnostic launch may be complicated and multifaceted, yet the benefits greatly outweigh the challenges. There are few other strategies that allow drug developers to reduce development time lines, increase the likelihood of R&D success, improve outcomes for patients and deliver greater value.

The challenges associated with the development and commercialization of personalized medicine can be minimized with proper and careful preparation, from development of biomarker strategy, to diagnostics partner selection and to engaging expanded stakeholder audiences – physicians, pathology labs, payers, patients, advocacy groups – at launch to ensure a therapy’s success.

Ultimately, companion diagnostics and personalized medicine have enormous potential to deliver significant value to patients and the health care system, benefiting all stakeholders.

❚ SURVEY POINTS TO BIOMARKERS’ EMERGING ROLE IN CLINICAL PRACTICE

According to InVentiv Health Consulting’s February 2017 survey: AMONG ONCOLOGISTS:

90%

believed multi-biomarker diagnostics will be the standard of care within the next 3–5 years.

64%

believed they will be testing about two-thirds of their patients with next-generation sequencing.

AMONG NON-ONCOLOGISTS

(including rheumatologists, pulmonologists, neurologists and PCPs):

Only 9%

reported low or very low familiarity with next-generation sequencing.

60%

believed that next-generation sequencing will be important or very important in informing treatment decisions in the next 3–5 years.

79%

believed there is a high or very high likelihood that they will be using biomarker assays for personalized medicine within the next 3–5 years, if available.

invivo.pharmamedtechbi.com

IV005045

Jessica B. Lee, PhD (jessica.lee@inventivhealth.com) is a director, Commercial Strategy and Planning, for inVentiv Health Consulting in San Francisco; Ravi Patel (ravi.patel@inventivhealth.com) is an engagement manager, Commercial Strategy and Planning, for inVentiv Health Consulting in New York; David Ruch (david.ruch@ inventivhealth.com) and Katya Magonova (katya.magonova@inventivhealth.com) are senior consultants in the Commercial Strategy and Planning practice for inVentiv Health Consulting, based in Boston and New York, respectively. The authors are members of the Commercial Strategy and Planning practice with inVentiv Health Consulting.

85%

stated that a diagnostic-therapy combination would increase their confidence in using the therapy due to: • Increased efficacy potential (58%) • Availability of new treatment options (45%) • Greater patient satisfaction (35%) • Improved safety potential (40%) • Increased confidence that the right patient will receive the right therapy (38%) AMONG ALL PHYSICIANS SURVEYED:

66%

believed that personalized therapies with an associated companion diagnostic will be available for many conditions outside of oncology within the next 5 years. invivo.pharmamedtechbi.com

â?š PERSONALIZED MEDICINE: Infographic

PERSONALIZED MEDICINE

There were 132 personalized medicines on the market in 2016, compared with just five in 2008. Herein, a look at some other key numbers in this rapidly growing field.

1 million

70%

Increase in personalized medicines in development from 2015 to 2020.

The number of volunteers from which the US Precision Medicine Initiative hopes to gather genomic data.

27%

of all NMEs approved by the FDA in 2016 are personalized medicines.

$5 billion

Estimated annual cost of wasted prescription drugs in the US.

$3 billion invivo.pharmamedtechbi.com

50%

of the personalized medicines approved by the FDA in 2016 are oncology drugs.

Estimated cost of wasted hospital cancer drugs.

DATA SUPPLIED BY: Datamonitor Healthcare Pharma intelligence |

Personalized Medicine Coalition

Strategic Transactions Pharma intelligence |

Biomedtracker Pharma intelligence |

invivo.pharmamedtechbi.com

PROBABILITY OF CLINICAL SUCCESS WITH OR WITHOUT SELECTION BIOMARKERS

2008-2015

100 PROBABILITY OF SUCCESS (%)

90

76.5%

76.7%

80

94.5% 83.9%

■ WITHOUT

invivo.pharmamedtechbi.com

PERSONALIZED MEDICINE: Infographic ❚

BIOMARKERS

■ WITH SELECTION

BIOMARKERS

70 63.0% 60

55.0% 46.7%

50 40

28.8%

30

25.9%

20

8.4%

10 0 PHASE I PHASE II

PHASE II PHASE III

$900 million

PHASE III NDA/BLA

NDA/BLA APPROVAL

PHASE I APPROVAL

Drug candidates in development with a diagnostic are three times more likely to gain approval than those without.

Amount raised in February 2017 by liquid biopsy play Grail Bio in the first tranche of its Series B round.

Total amount Grail, an Illumina spin-out, has raised since January 2016.

©2017 Informa Business Information, Inc., an Informa company

100,000

In England, the 100,000 Genomes Project aims to sequence the genomes of 100,000 National Health Service patients with rare diseases or cancer by the end of 2017.

Gayle Rembold Furbert

$1 billon

❚ DEALMAKING

❚ Deal-making

Covering deals made February 2017

Derived from Strategic Transactions, Informa’s premium source for tracking life sciences deal activity, the Deal-making column is a survey of recent health care transactions listed by relevant industry segment – In Vitro Diagnostics, Medical Devices, Pharmaceuticals, and Research, Analytical Equipment and Supplies – and then categorized by type – Acquisition, Alliance, or Financing.

Strategic Transactions is updated daily with in-depth deal analysis, structural and financial terms, and links to SEC-filed contracts.

For information about access please contact Customer Care at 800-332-2181 or ibislsales@informa.com

❚ IN VITRO DIAGNOSTICS Financings

Vermillion raises $5.6mm through private placement

❚ MEDICAL DEVICES Mergers & Acquisitions

To complement existing aesthetics business, Allergan acquires Zeltiq for $2.475bn Hologic buys Cynosure for $1.65bn cash Integra buys Codman Neurosurgery for over $1bn Ethicon buys GI device firm Torax Medical Merit Medical acquires critical care platform from Argon Medical Devices

Alliances

Biosimilars company Coherus BioSciences nets $117.5mm in FOPO

Arsanis gets global rights to panel of RSV antibodies from Adimab

Corium International nets $18.8mm in FOPO

Advaxis grants Sellas rights to its Lm Technology

Cymabay nets $9.4mm via FOPO

Astellas gets global rights to pneumococcus vaccine from Affinivax

Cytokinetics sells omecamtiv mecarbil royalty rights to Royalty Pharma for $100mm

Janssen Pharmaceutica licenses HIFtargeting compounds to Akebia

Evoke Pharma nets $7.5mm through follow-on

Amunix signs XTEN deal with Genentech

Novo AS invests €90.3mm into Evotec

Amygdala in-licenses rights to Gilead’s addiction candidate ApolloBio gets non-oncology rights to Inovio’s pre-cancer immunotherapy ASKA gets option to Pieris’ anemia candidate

Galena gets $16mm though public stock sale Sarepta sells priority review voucher to Gilead for $125mm Global Blood nets $136mm through upsized public stock sale Inventiva Pharma closes €42.7mm initial public offering

TerSera pays $250mm up front for US/ Canadian rights to AZ’s Zoladex

Solasia sub-licenses more supportive cancer care rights to Lee’s

Neovacs and BioSense Global enter licensing agreement for INF alpha program

Medtronic to distribute QT Vascular’s Chocolate PTA catheter worldwide

BI and Merck enter trial collaboration for Gilotrif + Keytruda

Wenzel Spine acquires PrimaLOK products from OsteoMed

Espero acquires Durlaza from New Haven Pharmaceuticals

Portola enters into $150mm royalty sale agreement with HealthCare Royalty Partners; gets $50mm up front

Financings

NeoPharm grants Hope Bioscience rights to preclinical cancer therapy

Pulmatrix nets $3.1mm via RDO

Public offering nets $7.4mm for Biostage

Seattle Genetics gets exclusive global rights to Immunomedics’ IMMU132 for solid tumors

Hill-Rom sells $300mm in notes to fund Mortara buy

❚ PHARMACEUTICALS Mergers & Acquisitions

LabCorp in discussions to acquire CRO PPD for over $8bn invivo.pharmamedtechbi.com

BioTime nets $18.9mm via FOPO

Janssen gets rights to Ablexis’ AlivaMab Mouse

Merit Medical acquires selected products from Catheter Connections

Arch Therapeutics nets $5.9mm through registered direct offering

Investor consortium acquires NexImmune

Alliances

Sanofi divests five consumer health care products to Ipsen Renova licenses stresscopin IND from Janssen Santen, twoXAR collaborate in ophthalmics Sobi gets rights to Valeant’s urea cycle disorder drug Ammonul

Moleculin nets $4.6mm in follow-on public offering Neos nets $23.5mm in FOPO Acasti nets $Cdn7.5mm via FOPO

Axovant gets $55mm in term loan from Hercules Sierra Oncology nets $24.7mm through public offering Synergy Pharmaceuticals nets $122mm via follow-on Windtree gets $10.5mm via PIPE Antibody company Xoma Corp. raises $25mm in RDO

❚ RESEARCH, ANALYTICAL

EQUIPMENT & SUPPLIES ONLINE ONLY

Reckitt Benckiser plans $16.7bn acquisition of Mead Johnson

Financings

Takeda spins off Japan consumer health care unit, operates under Takeda Consumer Healthcare division

Aldeyra nets $10.8mm via FOPO

Mergers & Acquisitions

Otolaryngology company Auris Medical nets $9.4mm in FOPO

Aviva grows proteomics business through acquisition of GenWay invivo.pharmamedtechbi.com

❚ IN VITRO DIAGNOSTICS Financings VERMILLION INC. Vermillion Inc. grossed $5.6mm through the private sale of 3.75mm common shares at $1.40 (a 6% premium). Investors also received five-year warrants to buy 2.8mm common at $1.80. The company develops and sells molecular diagnostics for ovarian cancer and other women’s health indications. (Feb.)

❚ MEDICAL DEVICES Mergers & Acquisitions ALLERGAN PLC ZELTIQ AESTHETICS INC. Allergan PLC is acquiring public body contouring device company Zeltiq Aesthetics Inc. for $56.50 per share (a 24% premium), valuing the deal at $2.475bn, almost seven times the company’s 2016 revenues of $354mm. (Feb.) Zeltiq was founded in 2005 and went public in 2011. The company’s main platform is covered by an extensive patent portfolio, much of which originated from Massachusetts General Hospital, where it was invented by Drs. Dieter Manstein and R. Rox Anderson. Zeltiq’s body contouring procedures use its controlled-cooling technology, CoolSculpting, which reduces the temperature of cold-sensitive fat cells in a targeted treatment area, killing them without damaging surrounding tissue.

The system contains a control unit and various applicators, designed for use on fat reduction in different parts of the body.

CoolSculpting first received FDA approval in September 2010 for love handles, and it subsequently gained clearance for under the chin, the back, the abdomen, the thighs, and underneath the buttocks.

The company hopes to expand marketed indications for CoolSculpting to additional areas of the body and is also researching its use in other markets such as dermatology, plastic surgery, aesthetics, and OB/GYN. The addition of Zeltiq’s body sculpting platform will add to Allergan’s plastic surgery and facial aesthetics lines, giving it a third business area within aesthetics. Allergan already sells silicone breast implants--and through the recent buy of LifeCell, gained the latter’s Accellular dermal matrices used in breast reconstruction--and has blockbuster franchises such as Botox and Juvederm in facial aesthetics (and within this space has in the past year and a half, acquired drug firms Topokine, Anterios, and Kythera).

Investment Banks/Advisors: Moelis & Co. (Allergan PLC); Guggenheim Partners LLC (Zeltiq Aesthetics Inc.)

HOLOGIC INC. CYNOSURE INC. Hologic Inc. is marking its entrance into the medical aesthetics market through the acquisition of Cynosure Inc. Hologic will pay $66 per share in cash (a 26% premium), giving the deal a $1.65bn equity value and an enterprise value of $1.44bn (net of cash). (Feb.) Cynosure was formed in 1991 and according the company, it is currently the number-one market share leader in the medical aesthetics space. Offerings include noninvasive body contouring (SculpSure diode laser), hair removal, vascular treatments, scar removal (PicoSure picosecond laser), wrinkle reduction (PelleFirm radiofrequency device), and skin revitalization.

Approximately 60% of the company’s business comes from physicians outside of the traditional plastic surgery and dermatology markets, with a focus on the ob/gyn market. Its flagship product in that area is the MonaLisa Touch fractional CO2 laser for vaginal rejuvenation. This market is highly complementary to that of Hologic, which offers diagnostics, breast biopsy equipment, mammography systems, and other women’s health products.

Cynosure’s market penetration in the gyn area is low, but Hologic believes through its own sales channels, it can boost market awareness for Cynosure’s products, while at the same time benefiting from Cynosure’s established sales presence in over 130 countries worldwide. Hologic is paying for the transaction with cash on hand, largely with proceeds of the recently announced $1.85bn divestiture of its blood screening business to Grifols. The deal with Cynosure was announced just one day after Allergan released details of its $2bn buy of aesthetics firm Zeltiq.

Hologic is quick to note that while the two companies are in competition with each other in the space, the timing of the acquisition announcements was coincidental. Hologic had been considering the Cynosure buy for a while, but its action at the time was spurred solely by Cynosure’s contact with Hologic after Cynosure received another acquisition bid from an undisclosed suitor. Investment Banks/ Advisors: Morgan Stanley & Co. (Hologic Inc.); Leerink Partners LLC (Cynosure Inc.) INTEGRA LIFESCIENCES HOLDINGS CORP. JOHNSON & JOHNSON DePuy Synthes Codman Neurosurgery In an effort to become the world’s leading provider of neurosurgical products, Integra LifeSciences Holdings Corp. is paying $1.045bn in cash to acquire Johnson & Johnson’s Codman Neurosurgery. (Feb.) Codman, which is part of DePuy Synthes, has created devices aimed at advanced hydrocephalus, neurocritical care, and electrosurgery. Products include Agility

©2016 Informa Business Information, Inc., an Informa company

guidewires, Accent occlusion balloons, Envoy guiding catheters, various brands of embolic coils (Enpower, Orbit Galaxy, Micrusphere, Cashmere, Deltapaq, Deltaplush, and Presidio), the ReVive peripheral vascular thrombectomy device, and neurodisposables. Its portfolio is complementary to Integra’s product offerings for tissue ablation, dural repair, and cranial stabilization. Codman’s products generated about $370mm in revenue for 2016. Just last month Integra agreed to acquire publicly held wound care firm Derma Sciences for over $201mm in cash. Investment Banks/ Advisors: Bank of America Merrill Lynch (Integra LifeSciences Holdings Corp.)

JOHNSON & JOHNSON Ethicon Inc. TORAX MEDICAL INC. Johnson & Johnson’s Ethicon Inc. is paying an undisclosed sum for closely held gastrointestinal device maker Torax Medical Inc. (Feb.) Torax’s portfolio is comprised of two products--the Linx reflux management system for the minimally invasive treatment of gastroesophageal reflux disease and Fenix continence restoration system for fecal incontinence. The Linx device is a safe and effective alternative to the currently used Nissen fundoplication surgical procedure for GERD. Torax raised over $80mm in its first five financing rounds and is backed by investors including Sanderling Ventures, the Mayo Foundation for Medical & Education Research, Thomas, McNerney & Partners, Accuitive Medical Ventures, Piper Jaffray Merchant Banking, Kaiser Permanente, and Johnson & Johnson Innovation. In its most recent round in August 2016, the firm pulled in $25mm through its Series E financing led

by Johnson & Johnson Innovation.

MERIT MEDICAL SYSTEMS INC. ARGON MEDICAL DEVICES INC. Merit Medical Systems Inc. acquired Argon Medical Devices Inc.’s critical care business. (Feb.) The acquired unit includes a manufacturing facility in Singapore and commercial operations in Japan. Argon manufactures specialty medical products for interventional radiology, vascular surgery, interventional cardiology, and critical care. The divestiture will allow Argon to focus on its higher growth interventional offerings.

Simultaneously Merit acquired selected assets from Catheter Connections Inc. The combined purchase price of the two transactions is valued at $48mm.

Alliances CATHETER CONNECTIONS INC. MERIT MEDICAL SYSTEMS INC. Merit Medical Systems Inc. acquired certain undisclosed products from Catheter Connections Inc. (Feb.)

invivo.pharmamedtechbi.com

DEALMAKING ❚

❚ DEALMAKING Catheter Connections markets the DualCap system which safely disinfects IV tubing end connectors and needle-free valves. The acquisition will expand Merit’s product offering and geographic presence. Merit manufactures disposable devices used in cardiology, radiology, and endoscopy. Simultaneously Merit agreed to acquire the critical care business of Argon Medical Devices Inc. The two purchases had combined annual revenues of $46mm and together sold for $48mm.

LEE’S PHARMACEUTICAL HOLDINGS LTD. SOLASIA PHARMA KK Solasia Pharma KK granted Lee’s Pharmaceutical Holdings Ltd. exclusive rights to market its oral mucositis product episil in the People’s Republic of China (PRC), Hong Kong, and Macau. The deal specifically excludes Taiwan, Beijing, Shanghai, and Guangzhou. (Feb.) An oral liquid supplied as a ready-to-use device, episil is indicated for oral mucositis in patients undergoing chemotherapy or radiation. The treatment forms a bioadhesive film to protect sensitive mucosal surfaces to help heal and reduce pain.

Solasia gained Japanese and PRC rights to episil from Camurus in 2015, and late last year, sublicensed the Japanese rights out to Meiji Seika Pharma. The deal is the second for Solasia and Lee’s in the supportive cancer care market. In 2015, Solasia granted Lee’s rights to sell the CINV product Sancuso in the PRC.

invivo.pharmamedtechbi.com

MEDTRONIC PLC QT VASCULAR LTD. QT Vascular Ltd. licensed Medtronic PLC worldwide rights to distribute its Chocolate PTA catheter for five years. The deal term will automatically renew for two additional one-year periods. (Feb.) The Chocolate PTA catheter incorporates a nitinol constraining structure to provide predictable and uniform balloon dilatation thus reducing trauma to the vessels.

The product--which is currently approved in the US, Europe, Australia, Turkey, Singapore and Hong Kong--can be used as a stand-alone treatment or adjunct treatment for stenosis in vessels above and below the knee. QT chose to partner with Medtronic because of its extensive global distribution network. QT Vascular’s TriReme Medical subsidiary currently sells the Chocolate PTA in the US along with a distribution partner. Sales will begin transitioning to Medtronic on a countryby-country basis, beginning in the US. OSTEOMED LLC WENZEL SPINE INC. Wenzel Spine Inc. acquired the PrimaLOK SP interspinous fusion and PrimaLOK FF facet fixation systems from OsteoMed LLC. (Feb.) PrimaLOK SP and PrimaLOK FF are intended for use in the minimally invasive

treatment of spinal disorders. PrimaLOK SP allows for optimal placement and fixation, ideally in the L5-S1 region of the spine, and is designed to accommodate anatomical variations without disrupting tissue. PrimaLOK FF consists of low-profile self-tapping screws for use in posterior fixation. Wenzel plans to integrate the polyaxial minimally invasive devices with its own pipeline of MIS offerings, which is currently in development. Following a limited US release, the company plans for a wider marketing push of the acquired PrimaLOK products during the second quarter of 2017.

Financings ARCH THERAPEUTICS INC. Arch Therapeutics Inc. netted $5.9mm through a registered direct offering of 10.17mm units priced at $0.60 (a 10% discount). Each unit consisted of one common share and 0.55 of a Series F warrant to purchase one common share (exercisable for five years at $0.75 per whole share). Arch develops hemostatic devices to control and stop bleeding and leaking resulting from surgery or trauma. (Feb.) BIOSTAGE INC. Biostage Inc. (bioengineered organ implants) netted $7.4mm through a public offering of 20mm common shares at $0.40. Investors also received warrants to purchase 20mm shares at $0.40. Rodman & Renshaw was the placement agent.

Funds will support R&D activities, including ongoing trials related to the company’s Cellframe biocompatible scaffold technology, which is used to create organ implants to treat conditions (including cancer) of the esophagus, bronchus, or trachea. (Feb.) Investment Banks/Advisors: Rodman & Renshaw Capital Group Inc. HILL-ROM HOLDINGS INC. Public medical device firm Hill-Rom Holdings Inc. privately sold $300mm in aggregate principal amount of senior unsecured notes due 2025 to fund its $330mm cash acquisition of Mortara Instrument Inc. (Feb.)

❚ PHARMACEUTICALS Mergers & Acquisitions LABORATORY CORP. OF AMERICA HOLDINGS PHARMACEUTICAL PRODUCT DEVELOPMENT INC. According to industry sources Laboratory Corp. of America Holdings (LabCorp) is in discussions to acquire contract research firm Pharmaceutical Product Development Inc. (PPD) for over $8bn including debt.

(LabCorp is one of the parties bidding in an auction for PE-owned PPD.) (Feb.) The transaction would be LabCorp’s larg-

est ever acquisition after having acquired CRO Covance Inc. in 2015 for $5.7bn. North Carolina based PPD was taken private in 2011 in a transaction valued at $3.9bn by PE firm The Carlyle Group and Hellman & Friedman. The company is one of the biggest clinical labs in the US and also has developed specialty testing including oncology testing, HIV genotyping/ phenotyping, diagnostic genetics and clinical trials. PPD employs over 18,500 people throughout 50 countries and works in a wide range of therapy areas including cardiology and urology. Back in January PPD spun-off X-Chem Inc., its small molecule biotech division into its own private company. The CRO space has heated up lately with the merger of Quintiles and IMS Holdings.

NEXIMMUNE INC. A consortium of private investors acquired private immuno-therapeutics firm NexImmune Inc. This group of investors was led by led by Sol J. Barer, PhD (chairman of Teva; formerly chairman and CEO of Celgene), and included Joshua Barer (managing director of VC firm Sunflower Life Sciences) and William A. Hawkins (former chairman and CEO of Medtronic).

Following the acquisition, a new board of directors--with former Schering-Plough CMO Robert Spiegel, MD, as chairman-was formed. (Feb.) The company appears to have received seed financing of approximately $5mm since its inception (from backers including New Enterprise Associates, Pfizer Venture, and Amgen Ventures) and was planning a Series A round with Sunflower, but alternatively went with the management buyout as a source of funding. Although no terms were disclosed, all outstanding NexImmune shares were purchased and the money will enable the biotech to reach an undisclosed milestone, according to COO Scott Carmer (who also joined the company board following the transaction).

NexImmune was established in 2011 and licensed its Artificial Immune (AIM) nanotechnology platform in 2012 from Johns Hopkins School of Medicine, where it was developed by Jonathan Schneck, MD, PhD, and Mathias Oelke, PhD. The technology uses synthetic nanoparticles known as artificial antigen-presenting cells (aAPCs), to which a magnetic field is applied to activate previously unresponsive T cells.

NexImmune’s platform replaces the damaged or dysfunctional T cells with aAPCs, which can be loaded with various tumorassociated antigens and co-stimulatory molecules, and are precisely engineered to produce in a patient a specific immune response. The AIM method has reduced toxicity versus chimeric antigen T cell (CAR-T) therapies. NexImmune’s pipeline includes preclinical candidates AIM ACT (a cell therapy for hematological malignaninvivo.pharmamedtechbi.com

cies) and AIM101 (an injectable vaccine for solid tumors), which both target CD8 T cells, as well as other preclinical compounds for autoimmune and infectious diseases. The company hopes to file an IND for its AIM-ACT candidate in November or December of this year.

RECKITT BENCKISER GROUP PLC MEAD JOHNSON NUTRITION CO. Reckitt Benckiser Group PLC is in discussions with Mead Johnson Nutrition Co. to the acquire public pediatric nutrition company for $90/share (a 23% premium), which would value the deal at about $16.7bn. (Feb.) Founded in 1905, Mead Johnson was acquired in 1965 by Bristol-Myers Squibb, which owned it up until 2009, when the Big Pharma spun it off as an independent company through a $684mm IPO followed by a share buyback. Mead Johnson--which mostly makes infant formulas under well-known brands Enfamil, Enfagrow, Nutramigen, and Enfapro--addresses infant nutritional needs such as healthy growth, brain and eye development, and iron supplementation, as well as issues, including protein allergies, metabolic disorders, colic, and gas. It also has other pediatric dietary supplements (e.g., Enfakid, Lactum, and Sustagen) targeting childhood recommended daily intake of nutrients and vitamins during specific stages of development up to age 12. With more than 70 products in over 50 countries, the company had 2016 net revenues of $3.7bn, with most (50%) of its sales coming from the Asian market, followed

by North America/Europe (33%), then Latin America (17%). Reckitt licensed Latin American rights to seven OTC products in the areas of pain, cough/cold, gastrointestinal, and dermatology from BMS in 2013. Since divesting its Indivior pharmaceuticals division in 2014, Reckitt has been focused on its consumer health, hygiene, and home care products. The addition of Mead’s infant formulas would add a new business segment for Reckitt and further boost its emerging market sales. Reckitt will finance the acquisition through a combination of cash and debt.

TAKEDA PHARMACEUTICAL CO. LTD. Takeda Consumer Healthcare Co. Ltd. Takeda Pharmaceutical Co. Ltd. is splitting off its Japan consumer health care business unit (JCHBU), and transferring it to a newly established division Takeda Consumer Healthcare Co. Ltd. (TCHC). (Feb.) Takeda, which created the division last year, says that TCHC is a more agile business, providing greater revenue and operations opportunities for JCHBU both within the Japanese OTC market and beyond. JCHBU had 2015 revenues of $720.6k and profits of $158k, with sales of products in over 15 markets. Leading

brands include the Alinamin vitamin line, Benza cold remedies, and Nicorette nicotine replacement therapies (in-licensed from GSK). The unit also sells therapies for GI ailments, motion sickness, ophthalmic care, skin care products, and medicated soaps/bath salts, as well as the Japanese health food Midori-no-Shukan. JCHBU will be operated by TCHC, with no changes in company names, locations, or staff.

Alliances ABLEXIS LLC JOHNSON & JOHNSON Janssen Biotech Inc. Ablexis LLC granted today Janssen Biotech Inc. a perpetual nonexclusive license to its AlivaMab Mouse platform for use in the discovery and development of antibody therapies. (Feb.) In exchange for the rights, Ablexis will receive an eight-figure up-front payment (Strategic Transactions assumes at least $10mm). Ablexis licensed the AlivaMab Mouse transgenic mouse technology from Aliva Biopharmaceuticals. Over the years Ablexis has signed similar nonexclusive licensing agreements with several Big Pharma companies, including Pfizer.

ADIMAB LLC ARSANIS BIOSCIENCES GMBH Arsanis Inc. Adimab LLC licensed Arsanis Inc. exclusive worldwide rights to develop and commercialize antibodies aimed at respiratory syncytial virus. (Feb.) Adimab will receive license fees, development milestones, and sales royalties.

Arsanis will first focus on selecting a lead RSV antibody candidate. The Bill & Melinda Gates Foundation concurrently provided Arsanis with a grant for up to $9.3mm to move the antibody through to IND filing. Under a previous 2013 agreement, Arsanis received rights to use Adimab’s platform to discover and optimize antibodies against a panel of clinically relevant anti-infective targets designated

by Arsanis. That deal has produced Phase II ASN100 for S. aureus pneumonia.

ADVAXIS INC. SELLAS LIFE SCIENCES GROUP Advaxis Inc. granted Sellas Life Sciences Group rights to use its Listeria bacteriabased Lm Technology in the development of Sellas’ Phase II cancer candidate galinpepimut-S. (Feb.) Advaxis’ platform bioengineers the Listeria bacteria so that it does not cause infection, but instead sees tumor cells as bacterial-infected cells, and prompts the body to launch an immune response to fight cancers. Sellas plans to apply the platform to galinpepimut-S, a WT1-targeted heteroclitic peptide antigen mixture. The compound is in various trials for acute

©2016 Informa Business Information, Inc., an Informa company

myeloid leukemia and malignant pleural mesothelioma (entering Phase III), multiple myeloma (Phase II), ovarian cancer and chronic myelogenous leukemia (Phase I/ II), and glioblastoma multiforme (entering Phase I/II). Advaxis will conduct preclinical studies up to IND filing, after which point Sellas will take over clinical trial and commercialization activities. Advaxis is eligible for up to $358mm in development, regulatory, and sales milestones, plus single to low-double-digit royalties.

AFFINIVAX INC. ASTELLAS PHARMA INC. Affinivax Inc. licensed Astellas Pharma Inc. exclusive worldwide rights to develop and commercialize a vaccine aimed at Streptococcus pneumoniae (pneumococcus). (Feb.) Affinivax will use its Multiple Antigen Presenting System (MAPS) to advance a pneumococcal disease vaccine, which is currently in preclinical studies. Astellas will lead and fund the development program and pay Affinivax $10mm up front, development and commercial milestones, and tiered sales royalties. The MAPS enables the high affinity binding of protective polysaccharides and proteins in a single vaccine. MAPS-based vaccines can potentially be better than currently available vaccines because of their ability to provide broader protection against diseases and due to their ability to reduce the first step in disease transmission.

AKEBIA THERAPEUTICS INC. JOHNSON & JOHNSON Janssen Pharmaceutica NV In a multi-year deal, Janssen Pharmaceutica NV licensed Akebia Therapeutics Inc. exclusive global rights to a library of hypoxia-inducible factor (HIF)-targeting compounds including JNJ5169, which Akebia has renamed AKB5169. (Feb.) Akebia pays $1mm in return for rights to compounds and related IP. Orally available AKB5169 is currently in preclinical studies for inflammatory bowel disease.

Those studies have shown that the compound may be highly differentiated from currently available systemic therapies because of its ability to reduce inflammation and promote mucosal healing at the disease site. Akebia will conduct additional preclinical studies and plans to submit an IND application in the next year to year-and-a-half. The other licensed HIF pathway compounds have potential for treating a variety of diseases. As part of the agreement, Johnson & Johnson Development Corp. received a common stock purchase warrant to buy 509,611 shares; the warrant is exercisable, in whole or in part, at any time prior to the fifth anniversary of the date of issuance with a payment to Akebia of up to $5mm.

invivo.pharmamedtechbi.com

DEALMAKING ❚

❚ DEALMAKING

invivo.pharmamedtechbi.com

AMUNIX OPERATING INC. ROCHE Genentech Inc. Amunix Operating Inc. signed a drug discovery and development agreement with Roche’s Genentech Inc. involving the former’s XTEN polymer linker technology. (Feb.) Amunix is no stranger to Big Pharma or top biotech partners, having previously teamed up with Eli Lilly, Janssen, Biogen, and Roche in XTEN deals. Most recently, Biogen exercised its option to license exclusive global rights to a recombinant Factor IX program in hemophilia. In the current alliance, Genentech pays an up-front fee, development and commercial milestones, and royalties. It will be responsible for selecting drug targets, but the therapeutic focus of the collaboration was not disclosed. Via high-yield microbial expression, the XTEN platform produces protein polymers that may be fused to therapeutic proteins to increase in vivo half-life. Among the advantages to user the linker technology including reduced dosing frequency, an increase in efficacy, and reduced side effects.

which is followed up by electroporation (using Inovio’s specialized device) to create pores in cell membranes and increase cellular uptake of the medicine. Inovio gets $3mm up front, $12mm when a Phase III pre-initiation clinical hold is lifted by the FDA, and up to $20mm in regulatory milestones, plus double-digit royalties.

ApolloBio could also make up to a $35mm equity investment in Inovio when the FDA hold is lifted (that amount could be lowered so that ApolloBio does not take majority ownership), and will pay for all development costs. ApolloBio was formed last year with a focus on in-licensing projects from American firms for commercialization in the Chinese market. Areas of interest include cancer, liver disease, and cardiocerebrovascular conditions.

AMYGDALA NEUROSCIENCES INC. GILEAD SCIENCES INC. Marking its first in-licensing (and first pipeline candidate), Amygdala Neurosciences Inc. licensed exclusive rights to Gilead Sciences Inc.’s GS6637 for substanceand behavior-based addictions. (Feb.) Amygdala was founded in 2015, but officially launches operations through this in-licensing. GS66374 (which has already been renamed ANS6637) is an aldehyde dehydrogenase 2 (ALDH2) inhibitor entering Phase II trials for addictive behaviors.

The compound works by preventing pathophysiologic dopamine surges and related cravings without altering basal dopamine levels. Gilead gained the project through its 2009 $1.28bn acquisition of CV Therapeutics. Amygdala plans to initiate Phase II studies during 2017 for cocaine and alcohol addiction.

ASKA PHARMACEUTICAL CO. LTD. PIERIS PHARMACEUTICALS INC. Pieris Pharmaceuticals Inc. granted ASKA Pharmaceutical Co. Ltd. an exclusive option to license Asian rights to its anemia candidate PRS080. ASKA’s rights could include Japan, South Korea, and certain other Asian markets, excluding China. (Feb.) Pieris gets $2.75mm up front and could receive up to $80mm in option exercise payments and milestones (for development and commercialization in an initial indication; additional payments could be realized for subsequent indications and additional territories), plus double-digit royalties up to the high-teens. PRS080 is a hepcidin inhibitor in development as an alternative to erythropoietin stimulating agents and iron supplements to treat anemia in hemodialysis-dependent chronic kidney disease patients. Pieris will conduct development up to Phase IIa, and once analysis is complete, AKSA can exercise its option. The deal is the second for both companies since the beginning of the year. In January, ASKA optioned rights to TesoRx’s preclinical oral testosterone replacement candidate for hypogonadism, and Pieris granted Servier rights to up to eight immuno-oncology compounds in a deal that could be worth up to $1.8bn.

APOLLOBIO CORP. INOVIO PHARMACEUTICALS INC. Inovio Pharmaceuticals Inc. granted ApolloBio Corp. exclusive rights to develop and sell its DNA immunotherapy VGX3100 in Greater China (China, Hong Kong, Macao, and Taiwan). The deal could be expanded to include Korea in three years. (Feb.) VGX3100 is a human papillomavirus-specific immunotherapy to treat pre-cancers caused by HPV. (Inovio is also developing it to treat HPV-related cancer, but ApolloBio’s rights are for pre-cancerous HPV infections and HPV-driven dysplasias; the alliance specifically excludes oncology indications.) The plasma DNA immunotherapy is administered via intramuscular injection,

ASTRAZENECA PLC TERSERA THERAPEUTICS LLC AstraZeneca PLC granted specialty pharma start-up TerSera Therapeutics LLC exclusive US and Canadian marketing rights to its cancer product Zoladex (goserelin).

AZ retains rights in the rest of the world, and will manufacture and supply the drug to TerSera. (Feb.) TerSera paid $250mm up front and committed to up to $70mm in sales milestones, plus mid-teens royalties. The product is the first in TerSera’s portfolio; the company was recently formed by CEO Edward Fiorentino and private equity firm GTCR, and plans to in-license late-stage and marketed therapies across a wide

range of indications including cancer, immunology, neurology, urology/gynecology, gastroenterology, rheumatology, and infectious diseases. The company is the third such venture for Fiorentino and GTCR; together they also formed Crealta Pharmaceuticals (acquired by Horizon Pharma in 2016) and Actient (bought

by Auxilium Pharmaceuticals in 2013).

Zoladex, an injectable LHRH agonist, is marketed for breast and prostate cancers, and is also indicated for endometriosis and uterine fibrosis. The product brought in $69mm in US and Canadian sales in 2016, and $816mm globally.

BIOSENSE GLOBAL LLC NEOVACS SA Neovacs SA granted BioSense Global LLC certain Asian rights to its Phase II interferon alpha kinoid (INFalpha kinoid) candidate for immune diseases. (Feb.) BioSense will make up to €65mm ($69mm) in up-front and milestone payments, and will also pay double-digit sales royalties.

Neovacs will complete the ongoing Phase IIb trial in systemic lupus erythematosus, after which point BioSense takes over and funds development and commercialization for lupus and the inflammatory skin disease dermatomyositis in China, Macao, Hong Kong, Taiwan, and Singapore. The company also gets right of first refusal in the licensed territories for any additional INFalpha kinoid indications, including Type I diabetes. Neovacs retains rights in the rest of the world excluding South Korea, where Chong Kun Dong holds a license under a late-2015 deal. The therapeutic vaccine was designed using Neovacs’ Kinoid technology, which chemically links a cytokine of interest (interferon alpha) to a foreign carrier protein (in this case, KLH--keyhole limpet hemocyanin).

The resulting kinoid generates polyclonal antibodies specific to each patient, causing the patient’s immune system to launch and regulate a response and effectively fight off the disease.

BOEHRINGER INGELHEIM GMBH MERCK & CO. INC. Boehringer Ingelheim GMBH and Merck & Co. Inc. entered into a trial collaboration to explore the combination of BI’s Gilotrif (afatinib) with Merck’s Keytruda (pembrolizumab) in a Phase II trial for locally advanced or metastatic squamous cell carcinoma (SqCC) of the lung. (Feb.) Gilotrif, an EGFR inhibitor, is marketed for SqCC lung cancer patients whose disease has progressed during or after treatment with a platinum-based chemo. (It is also in additional trials for other solid cancers including head and neck, brain, colorectal, cervical, esophageal, and pancreatic, among others. Keytruda, a PD-1 antibody, is on the market for melanoma and nonsmall cell lung cancer; approved for head invivo.pharmamedtechbi.com

❚ DEALMAKING and neck cancer; and awaiting approval for colorectal cancer and Hodgkin’s lymphoma. (Over two dozen trials are underway for various other blood and solid tumors.)

ESPERO PHARMACEUTICALS INC. NEW HAVEN PHARMACEUTICALS INC. Espero Pharmaceuticals Inc. acquired worldwide rights to New Haven Pharmaceuticals Inc.’s FDA-approved Durlaza (aspirin) extended-release capsules. (Feb.) Durlaza is the only once-daily drug of its kind indicated for the secondary treatment of stroke and acute cardiac events. The prescription product is designed to reduce the risk of death and myocardial infarction in patients with chronic coronary artery disease, and reduce the risk of death and recurrent stroke in people who’ve had an ischemic stroke or transient ischemic attack. Espero’s portfolio includes another cardiovascular drug, Gonitro (nitroglycerin) sublingual powder, which recently received FDA approval and is the only short-acting nitrate in a stabilized crystal granule form available in single dose packets.

invivo.pharmamedtechbi.com

HOPE BIOSCIENCES NEOPHARM CO. LTD. NeoPharm Co. Ltd. granted Hope Biosciences exclusive global rights to develop and sell its MERTK/AXL/pan-C-MET tyrosine kinase inhibitor, which Hope has named HOPE777. (Feb.) The preclinical candidate has potential at treating cancers resistant to EGFR-directed therapies, including erlotinib and gefitinib, and is in development for non-small cell lung, brain, and stomach cancers.

Hope plans to develop it as a monotherapy and as an immuno-oncology option in combination with checkpoint inhibitors, and intends to move it into clinical trials in 2018. The company, which was formed last year, is also working on HOPE888, an anti-nucleolin gemcitabine aptamer drug conjugate for leukemia that it recently licensed from AptaBio Therapeutics.

IMMUNOMEDICS INC. SEATTLE GENETICS INC. Immunomedics Inc. granted Seattle Genetics Inc. exclusive global rights to develop, fund, manufacture, and sell IMMU132 (sacituzumab govitecan) for solid tumors.

Immunomedics retains the right to copromote in the US (if it participates in 50% of the sales efforts). (Feb.) IMMU132 is an immunoconjugate of the human mAb hRS7 and SN38 (the active metabolite of irinotecan). Immunomedics developed it using its DOCK-AND-LOCK protein conjugation technology, and has the candidate in Phase II trials for a variety of solid tumors including breast, colorectal, stomach, lover, non-small cell and small cell lung, pancreatic, prostate, head and neck, renal, ovarian, esophageal, bladder, cervical, and endometrial cancers. Seattle

Genetics paid $250mm up front and took a 2.8% stake in Immunomedics through the purchase of 3mm common shares at $4.90 (an 11% premium). It also gets a three-year warrant to buy 8.66mm shares at the same price, which if exercised, could bring the company’s stake up to 9.9%. Immunomedics is eligible for an additional $50mm payment (or negotiated economic splits) related to rights outside the US, Canada, and EU, and could also get up to $1.65bn in development, regulatory, and sales milestones, plus tiered double-digit royalties. Included in the milestone figure is a potential near-term payment related to BLA acceptance related to a triple-negative breast cancer (TNBC) indication; Seattle Genetics is responsible for initiating Phase III trials and submitting the BLA for accelerated approval. Seattle Genetics will continue all ongoing trials, but the initial focus will be on breast cancer. (If approved by the FDA, IMMU132 could be the first to market specifically for triple-negative breast cancer.) The companies will form a joint steering committee chaired by a representative from Seattle Genetics. Immunomedics has had IMMU132 in clinical trials for three years, and in December 2015 began a competitive strategic process exploring licensing opportunities for the project. Seattle Genetics was one of over 30 companies to get information on IMMU132 and was the first to get its alliance offer approved; Immunomedics, however, has left the door open for additional negotiations from other parties still involved in the process. It has until February 19 to accept a superior proposal if one is presented. If it takes another offer, it has to pay Seattle Genetics a termination fee. Investment Banks/Advisors: Greenhill & Co. Inc. (Immunomedics Inc.) IPSEN SANOFI In order to satisfy requirements from the European Commission related to Sanofi’s recently closed business swap with Boehringer Ingelheim GMBH, Sanofi divested five consumer health care (CHC) products to Ipsen, which paid €83mm ($88.3mm).

The products are marketed in Europe. (Feb.) In December 2015, Sanofi and BI penned a deal through which BI would gain control of Sanofi’s animal health business Merial, and in exchange, Sanofi would take over BI’s CHC business. (The transaction closed last month.) Sanofi is now off-loading some of its products per the EC’s request.

Ipsen gets Prontalgine (acetaminophen/ caffeine/codeine), an OTC headache pain therapy sold only in France; Buscopan (hyoscine butylbromide), an antispasmodic for irritable bowel syndrome marketed in the Czech Republic, Estonia, Hungary, Latvia, Polana, and Slovakia; Suppositoria Glycerini (glycerin suppository), a laxative sold in the Czech Republic; and the carbocysteine-based expectorants Mucothiol (Greece) and Mucodyne (Ireland) for

cough/flu/respiratory ailments. Manufacturing for all of the acquired products will be provided by an undisclosed third party.

JOHNSON & JOHNSON Janssen Pharmaceuticals Inc. RENOVA THERAPEUTICS Janssen Pharmaceuticals Inc. has transferred the US investigational new drug (IND) file for stresscopin to Renova Therapeutics Inc. (Feb.) Stresscopin is a hormone involved in responses to physiological stress. Renova has renamed the in-licensed peptide infusion therapy RT400 and will continue developing it in Phase II trials for acute decompensated heart failure. In January 2016, Renova received exclusive worldwide rights to stresscopin genes and select peptides and proteins from the Research Development Foundation.

SANTEN PHARMACEUTICAL CO. LTD. Santen Inc. TWOXAR INC. Santen Pharmaceutical Co. Ltd.’s US subsidiary Santen Inc. is teaming up with twoXAR Inc. in the discovery and development of drug candidates for glaucoma. (Feb.) TwoXAR will use its DUMA computational drug discovery platform to discover, screen, and prioritize compounds aimed at glaucoma. Ophthalmic-focused Santen gets exclusive global rights to develop and commercialize any resulting candidates. DUMA is a cloud-based solution that utilizes artificial intelligence to find associations between drug and disease.

SWEDISH ORPHAN BIOVITRUM AB VALEANT PHARMACEUTICALS INTERNATIONAL INC. In a three-year deal, Valeant Pharmaceuticals International Inc. licensed Swedish Orphan Biovitrum AB (Sobi) exclusive rights to sell and distribute Ammonul (sodium phenyl acetate and sodium benzoate) injection in Europe, the Middle East, and North Africa. (Feb.) The deal will last until the end of 2019. Ammonul is FDA approved for acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle. It’s not registered in the EU or MENA regions however it is available under named patient use programs. The new tie-up replaces the current distribution agreement with Valeant Pharmaceuticals North America for the same territory.

Financings ALDEYRA THERAPEUTICS INC. Aldeyra Therapeutics Inc. (developing therapies for diseases related to aldehydes) netted $10.8mm in a follow-on public offering of 2.56mm common shares (including the overallotment) at $4.50 each. The company plans to use the proceeds for ongoing clinical trials invivo.pharmamedtechbi.com

for candidates including topical ADX102 (Phase III in noninfectious anterior uveitis and Sjögren-Larsson Syndrome; Phase IIb in allergic conjunctivitis; Phase IIa in dry eye syndrome; Sjögren-Larsson Syndrome, and SSADH deficiency), ADX103 (Phase IIa in dry eye syndrome), ADX104 (Phase 2II in Sjögren-Larsson Syndrome and SSADH deficiency), and a Phase I trial of systemically administered ADX102 or ADX104. (Feb.) Investment Banks/Advisors: Canaccord Genuity Inc.; Laidlaw & Co.; Stifel Nicolaus & Co. Inc. AURIS MEDICAL HOLDING AG Auris Medical Holding AG (otolaryngology therapeutics; lead candidate Keyzilen for acute inner ear tinnitus) netted $9.4mm in a follow-on public offering of 10mm units at $1.00; each unit consisted of one common share and one warrant entitling the holder to purchase 0.70 of a common share at $1.20 per whole share for a period of five years. The company also sold 1.35mm additional warrants in a partial exercise of the overallotment option. Auris will use the offering proceeds for general corporate purposes. (Feb.) Investment Banks/Advisors: Maxim Group LLC; Roth Capital Partners BIOTIME INC. Just days after licensing ophthalmic IP from the University of Pittsburgh Medical Center, regenerative medicine firm BioTime Inc. netted $18.9mm through the follow-on public sale of 7.45mm common shares (including the overallotment) at $2.70. (Feb.) Investment Banks/Advisors: Chardan Capital Markets; Ladenburg Thalmann & Co. Inc.; LifeSci Capital LLC; Raymond James & Associates Inc. COHERUS BIOSCIENCES INC. Coherus BioSciences Inc. (biosimilars) netted $117.5mm in a follow-on public offering of 5.2mm common shares at $24.25. The company will use the proceeds from the offering to fund sales, marketing and manufacturing for CHS1701 (pegfilgrastim biosimilar for febrile neutropenia) and for manufacturing and clinical trials for CHS0214 (etanercept biosimilar for ankylosing spondylitis, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis and rheumatoid arthritis; partnered with Daiichi Sankyo in Japan) and CHS1420 (adalimumab biosmilar for ankylosing spondylitis, Behçet’s Disease, Crohn’s Disease, juvenile idiopathic arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis). (Feb.) Investment Banks/Advisors: BMO Financial Group; Citigroup Inc.; Cowen & Co. LLC; JP Morgan & Co. CORIUM INTERNATIONAL INC. Corium International Inc. (transdermal and transmucosal drug delivery) netted $18.8mm in a follow-on public offering of

6.7mm shares at $3. The company will use the offering proceeds for product development including for R&D, to pay down debt, and for potential acquisitions. (Feb.) Investment Banks/Advisors: Cantor Fitzgerald & Co.

now use the cash from the sale to support development of additional exon skipping candidates and enhancement of the company’s antisense platform. (Feb.) Investment Banks/Advisors: Credit Suisse Group (Sarepta Therapeutics Inc.)

CYMABAY THERAPEUTICS INC. CymaBay Therapeutics Inc. (orphan diseases) netted $9.4mm through the follow-on sale of 5.18mm common shares at $1.93. The company will use the funds for ongoing development of seladelpar, which is in Phase II for primary biliary cholangitis and homozygous familial hypercholesterolemia. (Feb.) Investment Banks/Advisors: LifeSci Capital LLC

GLOBAL BLOOD THERAPEUTICS INC. Global Blood Therapeutics Inc. (developing drugs for blood-based diseases including sickle cell disease (SCD) and idiopathic pulmonary fibrosis) netted $136mm through the public offering of 5.9mm common shares (including the overallotment) at $24.50. (The company had originally hoped to bring in $75mm.)

Money will go towards pipeline activities, including work on lead candidate GBT440, in Phase I/II for SCD. (Feb.) Investment Banks/Advisors: Cantor Fitzgerald & Co.

CYTOKINETICS INC. Royalty Pharma is paying Cytokinetics Inc. $90mm in cash and $10mm in stock (875,656 shares at $11.42; a 9% premium) for a 4.5% royalty on global sales of omecamtiv mecarbil. Under certain circumstances the royalty rate may increase to 5.5%. (Feb.) Investment Banks/Advisors: Centerview Partners LLC EVOKE PHARMA INC. Evoke Pharma Inc. (therapies for gastrointestinal diseases) netted $7.5mm through a follow-on public offering of 2.8mm common shares (including the overallotment) at $2.90 each. The company will use the funds for ongoing Phase III trials for its gastroparesis candidate Gimoti and for pre-commercialization activities including the NDA submission. (Feb.) Investment Banks/Advisors: Laidlaw & Co. EVOTEC AG Drug discovery firm Evotec AG received a €90.3mm ($96.4mm) investment from new buyer Novo AS, which purchased 13mm shares at €6.84 (a 4% discount).

Proceeds will support Evotec’s focused innovation and roll-up strategy surrounding its drug discovery platforms and collaborations. (Feb.) GALENA BIOPHARMA INC. Galena Biopharma Inc. (oncology and hematology therapies) netted $16mm through the public sale of 17mm common shares at $1.

Investors also received five-year warrants to purchase 17mm shares at $1.10. (Feb.) Investment Banks/Advisors: Canaccord Genuity Inc. GILEAD SCIENCES INC. SAREPTA THERAPEUTICS INC. Sarepta Therapeutics Inc. sold its rare pediatric disease priority review voucher (PRV) to Gilead Sciences Inc. for $125mm.

Sarepta was granted the PRV when Exondys51 was approved by the FDA for patients with Duchenne muscular dystrophy amenable to exon skipping, and will

©2016 Informa Business Information, Inc., an Informa company

INVENTIVA PHARMA Inventiva Pharma (developing treatments for fibrosis and rare/orphan diseases) netted €42.7mm ($45mm) through its initial public offering on Compartment C of Euronext. The company sold 5.65mm new shares at €8.50. (Feb.) Investment Banks/Advisors: KBC Securities; Societe Generale MOLECULIN BIOTECH INC. Moleculin Biotech Inc. (cancer therapies) netted $4.6mm through the public offering of 3.7mm units at $1.35 apiece. Each unit consisted of one common share; a five-year Series A warrant to purchase 0.50 of a common share exercisable at $1.50; a 90-day Series B warrant to buy one common share exercisable at $1.35; and a five-year Series C warrant to purchase 0.50 of a common share exercisable at $1.50. This is Moleculin’s first public offering since the company completed its $8.6mm IPO in June of last year. (Feb.) Investment Banks/Advisors: National Securities Corp.; Roth Capital Partners NEOS THERAPEUTICS INC. Neos Therapeutics Inc. netted $23.5mm through the public offering of 5mm common shares at $5mm. The company will use the proceeds to back commercialization efforts for Adzenys (amphetamine), an extended-release, orally disintegrating tablet (XR-ODT), which was FDA approved in January 2016 for attention deficit hyperactivity disorder (ADHD)). Additionally, the company will use funds to support potential launches of other ADHD candidates Cotempla XR-ODT (methylphenidate; NDA resubmitted December 2016) and NT0201 XR oral suspension (amphetamine; NDA submitted in November 2016), if approved. Monies raised will also enable further development of additional pipeline compounds. (Feb.) Investment Banks/Advisors: BMO Financial Group; Cowen & Co. LLC; JMP Securities LLC

invivo.pharmamedtechbi.com

DEALMAKING ❚

❚ DEALMAKING NEPTUNE TECHNOLOGIES & BIORESSOURCES INC. Acasti Pharma Inc. Cardiovascular-focused Acasti Pharma Inc. netted $Cdn7.5mm ($5.7mm) through the follow-on public sale of 5.5mm units priced at $Cdn1.45. Each unit consists of one Class A share and half of one common share purchase warrant; a whole warrant can buy one share of common stock at $Cdn2.15. The company will use the funds to finish manufacturing scale-up and the upcoming Phase III trial for its cholesterol medicine CaPre. (Feb.)

SYNERGY PHARMACEUTICALS INC. Synergy Pharmaceuticals Inc. (gastrointestinal disease therapeutics) netted $122mm through the follow-on public offering of 20.3mm common shares at $6.15. The company will use the proceeds to help fund commercial activities for its chronic idiopathic constipation drug Trulance, and for ongoing Phase III trials of plecanatide for irritable bowel syndrome with constipation. (Feb.) Investment Banks/Advisors: Canaccord Genuity Inc.; Cantor Fitzgerald & Co.; HC Wainwright & Co.

PORTOLA PHARMACEUTICALS INC. Portola Pharmaceuticals Inc. (therapies for thrombosis and other blood disorders) entered into a $150mm royalty sale agreement with HealthCare Royalty Partners (HCRP) pursuant to which HCRP will purchase royalties on future sales of Portola’s Factor Xa inhibitor antidote AndexXa (andexanet alfa). The candidate completed Phase III trials, and Portola is currently preparing a BLA resubmission following receipt of a Complete Response Letter from the FDA; an MAA for approval in the EU is pending. (Feb.)

WINDTREE THERAPEUTICS INC. Respiratory drug developer Windtree Therapeutics Inc. (formerly Discovery Laboratories) raised $10.5mm through a private placement of 7,049 Series A convertible preferred stock units at $1,495 to new and returning shareholders. Each unit consists of one Series A convertible preferred share (converts into 1,000 common shares) and 1,000 Series A-1 seven-year warrants to buy one common share at an exercise price of $1.37. The company will use the proceeds to fund the Phase IIb trial of Aerosurf in premature infants with respiratory distress syndrome. (Feb.)

PULMATRIX INC. Inhaled therapies developer Pulmatrix Inc. netted $3.1mm through the registered direct offering of 950k common shares at $3.50 each to institutional investors. The company will use the proceeds to make monthly principal and interest payments related to the loan agreement signed with Hercules in mid-2015.

Pulmatrix netted $4.7mm via an RDO just several days prior to this financing. (Feb.) Investment Banks/Advisors: Rodman & Renshaw Capital Group Inc.

invivo.pharmamedtechbi.com

ROIVANT SCIENCES LTD. Axovant Sciences Ltd. Axovant Sciences Ltd. (dementia therapeutics) entered a $55mm term loan agreement with Hercules Capital, which funded the full amount upon closing. Axovant also issued Hercules a seven-year purchase warrant for up to 274k common shares at an exercise price of $12.04. The loan, which matures March 1, 2021, is repayable as interest only for 18 months, but that period may be extended to 24 months if Axovant meets specific development milestones. (Feb.) SIERRA ONCOLOGY INC. Sierra Oncology Inc. (formerly ProNAi Therapeutics; cancer treatments based on the DNA damage response (DDR) network) netted $24.7mm through the public sale of 19.5mm common shares at $1.35.

Proceeds will fund continued development of lead candidate SRA737, a checkpoint kinase 1 inhibitor in Phase I trials, and SRA141, a cell division cycle 7 kinase inhibitor in preclinical studies. (Feb.) Investment Banks/Advisors: Jefferies & Co. Inc.; SunTrust Banks Inc.; Wedbush PacGrow Life Sciences

In Vivo

Pharma intelligence |

executive editors Nancy Dvorin, Managing Editor John Hodgson, Data Editor William Looney, Pharma Editor Ashley Yeo, Medtech Editor

editorial staff Peter Charlish Jessica Merrill Amanda Micklus Sten Stovall

contributing editors Deborah Erickson Regina Paleski Mark Ratner Marc Wortman

research manager Steven Muntner

deals analysts

Beth Detuzzi, Deanna Kamienski Maureen Riordan

design supervisor

Gayle Rembold Furbert

senior designer Janet Haniak

designers

Jean Marie Smith, Paul Wilkinson

XOMA CORP. Xoma Corp. (antibody therapeutics) raised $25mm in a registered direct offering of 1.2mm common shares and 5k convertible preferred shares to Biotechnology Value Fund L.P. Each common share was purchased at $4.03 (6.5% discount) and each preferred share at $4,030 (convertible into 1k common shares). The company will use the proceeds to fund the clinical development of XOMA358 (allosteric modulating monoclonal antibody which binds to insulin receptors); for other preclinical and regulatory activities for other candidates; and to repay a term loan to Hercules Technology III LP. (Feb.)

head of in vivo Karen Coleman

advertising

Christopher Keeling

corporate sales

John Lucas, Elissa Langer Alicia McNiven

technology operations manager Chris Trudeau

vp, e-strategy & development Adam Gordon

managing director Phil Jarvis

editorial office 52 Vanderbilt Avenue, 11th floor New York, NY 10017 www.InVivo.PharmaMedtechBI.com customer service clientservices@pharmamedtechbi.com

In Vivo [ISSN 2160-9861] is published monthly, except for the combined July/August issue, by Informa Business Intelligence, Inc., 52 Vanderbilt Avenue, 11th Floor, New York, NY 10017. Tel: 888-670-8900 (US); +1-908-547-2200 (outside US); Fax: 646-666-9878.

Office of publication, The Sheridan Group, 66 Peter Parley Row, Berlin, CT 06037. Postmaster: Send address changes to Informa Business Intelligence, 52 Vanderbilt Avenue, 11th floor, New York, NY 10017. ©

2017 by Informa Business Intelligence, Inc., an Informa company.

All rights reserved.

No part of this publication may be reproduced in any form or incorporated into any information retrieval system without the written permission of the copyright owner.

invivo.pharmamedtechbi.com