IMPACT 2025: MassBiologics of UMass Medical School Strategic Plan 2020-2025

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M AS SBIOLOGICS STR ATEGIC PL AN IMPAC T 2025

MassBiologics O F TH E U N IVE RS IT Y O F M AS SACH U S E T T S M E D I C A L SCH O O L

MOVING FORWARD

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STR ATEGIC PL AN IM PAC T 2025

MassBiologics

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O F T H E U N I V E R S IT Y O F M A S S AC H U S E T T S M E D I C A L S C H O O L

MISSION

To discover, develop and manufacture affordable biological medicines that improve the lives of people in the Commonwealth of Massachusetts and around the world while educating and training a workforce that will perpetuate this public health mission.

M AT TA PA N

M AT TA PA N

FA LL R IVE R


M AY 2020

AS MASSBIOLOGICS OF THE UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL CELEBRATES 125 YEARS of innovations and impact on health and completes a successful six-year strategic plan, we turn to consider the future. Toward that end, MassBiologics of UMMS has coordinated its strategic planning effort with the process undertaken by UMMS. Two fundamental questions have guided both strategic planning efforts:

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Where do we want to be in 2025?

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How will we get there?

As part of that coordinated effort, MassBiologics convened four work groups to identify key questions and future directions.

1 The working groups deliberated in four priority areas:

DISCOVERY & TRANSLATIONAL /CLINICAL RESEARCH

GLOBAL IMPACT

Each working group collected and reviewed historical and contemporary information in order to formulate recommendations relevant to the following questions: What are the priorities for developing the current pipeline of medicines, what new medicines should we pursue and how should we expand our research platforms to support translation of UMMS discoveries? How can we maximize the global impact on health of current and future licensed products and how do we best evaluate the impact of new medicines? How do we optimize recruitment and retention of top talent and, as an integral part of UMMS, how do we best participate in workforce development across the spectrum of skills needed for biologics discovery, development and manufacturing? How do we grow the contract development and manufacturing portfolio, what are our priorities

EDUCATION & TRAINING

OPERATIONAL EXCELLENCE & FINANCIAL STEWARDSHIP

for developing new capabilities and services, and what collaborations should we pursue to add value to the translational medicine achievements of UMMS? Following the working groups’ deliberations, a facilitated retreat was held to engage a broad group of UMMS stakeholders to chart the future course of MassBiologics for continued success and alignment with the overall priorities of UMMS. Based on presentations from each of the working groups, vigorous dialogue with the leadership of UMMS and reflections on the characteristics that have sustained MassBiologics of UMMS for over 125 years as an innovator in biologics, we reaffirm our mission and provide a strategic plan to guide the next five years of creating Medicines for Better Lives.


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STRATEGIC

GOAL

DISCOVERY & TRANSLATIONAL/ CLINICAL RESEARCH Enhance innovation and increase impact by advancing the science of translation and channeling more discoveries into development and clinical practice. MassBiologics of UMMS has all the capabilities and expertise that are required for the translation of intramural discoveries through preclinical development, manufacturing process development, quality control and quality

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assurance, cGMP facilities and manufacturing, regulatory affairs and clinical research leading to licensure, commercialization and health impact of its discoveries.

Discovery efforts over the last five years have resulted in a robust pipeline of high-impact medicines including the following: LYME PREP - a human monoclonal antibody to prevent Lyme disease

RAB1/RAB3 - human monoclonal antibodies for rabies post exposure prophylaxis in North America

S315 - a human monoclonal antibody to treat diphtheria

PERTUSSIS VACCINE - a next-generation pertussis vaccine that prevents colonization as well as symptoms of severe pertussis in children and adults

HUMAN MONOCLONAL SECRETORY IGA (SIGA) antibodies and single domain antibodies (VHH, nanobodies) to prevent childhood and traveler’s diarrhea

OLIGONUCLEOTIDE THERAPIES for ALS and other diseases, in conjunction with UMMS and the Warren Alpert Foundation


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IN THE COMING YEARS we seek to advance these new medicines into clinical practice while maintaining a broad and vigorous pipeline of innovative products and technical services. MassBiologics will continue its focus on the most pressing contemporary unmet medical needs, leveraging collaborations and funding from public and private organizations with the same goals, such as CDC, NIH, DARPA, WHO and the Bill & Melinda Gates Foundation. In addition, the highly competitive environment of contract manufacturing necessarily drives a synergy between MassBiologics’ discovery, process development and manufacturing capabilities that will enable innovative technology platforms to optimize the discovery and development of the pipeline. Building our intramural pipeline around MassBiologics’ expertise in monoclonal antibody, viral vectored and oligonucleotide therapeutics will ensure that we can address unmet medical needs with the most advanced technologies.

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Major Milestones

At the same time, we seek to optimize access to MassBiologics’ translational capabilities in order to advance more UMMS discoveries toward becoming licensed products. We are well positioned to provide support for UMMS translational researchers and clinician-scientists along the product development pipeline from discovery to preclinical development and early stage clinical trials. We will need to expand technology platforms and expertise that harmonize with the needs of UMMS investigators for drug discovery, development and manufacturing. By providing concierge translational services, in specific areas of expertise, MassBiologics in collaboration with UMMS and the Advanced Therapeutics Initiative, will accelerate the translation of UMMS researchers and clinician-scientists’ discoveries through development and into early stage clinical trials. We will leverage MassBiologics’ capabilities in preclinical development, process development, quality control

and quality assurance, cGMP manufacturing, regulatory affairs, and clinical research. As we expand our technology and manufacturing platforms to better harmonize with discoveries emerging from UMMS, we will also create opportunities to combine advanced therapeutics platforms with our expertise in monoclonal antibody discovery and vaccines. In particular, we anticipate increasing opportunities for viral and nonviral vectoring of multiple classes of therapeutics including nucleic acids. We have identified a robust pipeline of UMMS discoveries to target translation to the clinic including the following; • Antisense oligonucleotide for the treatment of amyotrophic lateral sclerosis (ALS) to selectively silence SOD1 and C9orf72 • AAV2 to replace alpha 1 antitrypsin production for the treatment of alpha 1 antitrypsin deficiency

We have established the following major milestones to guide the first year of our Discovery and Translational/Clinical Research strategic goal.

S315- Present Phase I clinical trial results to FDA Lyme PrEP - Complete preclinical studies sIgA antibodies - Complete preclinical studies, file investigational new drug application with FDA Single domain antibodies (VHH, nanobodies) Preclinical development to select lead VHH Rab1/Rab3 - Complete preclinical studies Pertussis vaccine - Continue preclinical development

Establish IND Navigator within Advanced Therapeutics Initiative Establish project management capability within Advanced Therapeutics Initiative Establish Advanced Therapeutics Initiative administrative office policy and procedures Identify barriers, define internal funding model and develop specific project plans Manufacture cGMP batch of ASO for selectively silencing of SOD1 and C9orf72

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STRATEGIC

GOAL

GLOBAL IMPACT

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Measurably improve the health and welfare of the residents of Massachusetts and the citizens of the world by discovering, developing and promoting public health interventions for the benefit of those greatest in need. During its 125 year history, MassBiologics of UMMS has had a profound impact on human health through development of licensed products that address unmet medical needs and through supporting the development of innovative medicines by extramural organizations that utilize MassBiologics’ Contract Development and Manufacturing Organization. The National Institutes of Health sponsored nonhuman primate reagent resource

(NHPRR) provides novel primate antibodies in support of federally-funded research. One approach to describing the impact of the currently licensed medicines that MassBiologics has discovered and developed is to look at the unmet medical needs that these medicines address and where these medicines are distributed. The indications for the five currently licensed MBL related medicines are shown in the table below:

Licensed Medicines

Indication

TDVAX

Prevention of diphtheria and tetanus

CYTOGAM

Prophylaxis of cytomegalovirus disease associated with transplantation of kidney, lung, liver, pancreas and heart

SYNAGIS

Prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients

ZINPLAVA

Reduce recurrence of Clostridium difficile infection (CDI) in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence

RABISHIELD

Prevention of rabies after exposure

Reagents Use Nonhuman Primate Reagent Resource

Primary supplier of high quality reagents to facilitate the optimal use of Nonhuman primate models in biomedical research (funded through NIH)

Adjuvant Toxoids

Safe and effective adjuvants for human and veterinary vaccines

All five licensed medicines prevent life-threatening infections that occur around the globe and the NHPRR facilitates the discovery of more new medicines. TDVAX was first licensed in the United States in 1972 and MassBiologics provides 100 percent of this vaccine to the Commonwealth of Massachusetts and approximately 60 percent of the supply to the remainder of the United States. TDVAX has also been used in Australia, Asia,

Eastern and Western Europe, and the Caribbean to address emergency shortages and natural disasters. Each of the four antibody-based medicines, Cytogam, Synagis, Rabishield and Zinplava, is the only biologic medicine that is available to prevent life-threatening infections with CMV, RSV, rabies or recurrence of C. difficile infection.


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OUR VISION FOR MAXIMIZING the impact on health of the medicines we develop and the services we provide to optimize translation of UMMS discoveries into clinically important medicines is rooted in a long history of taking action to address unmet medical needs, especially for economically disadvantaged populations. For TDVAX, we seek to maximize the health impact by widening the distribution of TDVAX, a vaccine listed on the World Health Organization’s essential medicines list, to eradicate neonatal tetanus and to decrease the risk of diphtheria outbreaks. This will require expansion into international markets to improve global coverage. It will also require renewed attention to lowering the cost of goods to make TDVAX more affordable. The next medicine in the pipeline that will have a global impact is the MassBiologics human diphtheria antitoxin (S-315). Currently completing

a Phase I clinical trial, further development of MassBiologics human diphtheria antitoxin (S-315) into a licensed medicine would replace equine DAT around the world. To do this, we will focus on developing proactive alliances with industry, governments and non-government organizations (e.g. WHO, PAHO, MSF, GAVI and IAVI) to increase the global impact of our discoveries. Two additional therapies that have been manufactured and are finishing preclinical testing are Lyme PrEP, for the prevention of Lyme disease, and sIgA for the treatment of enterotoxigenic Escherichia coli (ETEC) infection. As the number of reported cases of Lyme disease increases by more than 300,000 per year, MassBiologics discovered and developed a single human monoclonal antibody that prevents infection in animals that are exposed to the bite of ticks carrying Borrelia burgdorferi, the bacteria that causes

Lyme disease. A yearly injection of this antibody is expected to provide Pre-Exposure Prophylaxis against Lyme disease (Lyme PrEP) in upcoming human clinical trials. ETEC causes more than 800 million infections worldwide. Through collaborations spearheaded by the Bill & Melinda Gates Foundation, MassBiologics has developed a secretory IgA that will be manufactured in rice and provided as a food supplement for the United States and developing world. For MassBiologics to optimize translation of UMMS discoveries toward becoming licensed medicines and rapidly achieve value enhancing milestones, we seek to enhance the interface between UMMS investigators engaged in discovery and development with MassBiologics’ translational and manufacturing expertise. Continued

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Global distribution of MassBiologics’ lifesaving medicines and reagents

TDVAX Td vaccine for Tetanus and Diphtheria

CYTOGAM Anti-CMV IgG

SYNAGIS Anti-RSV mAb

ZINPLAVA Ant-C. diff mAb

RABISHIELD Anti-Rabies mAb

Nonhuman Primate Reagent Resource

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Major Milestones

We have established the following major milestones to guide the first year of our Global Impact strategic goal.

Develop regulatory strategy for TDVAX in Canada. Identify and secure a partner for TDVAX in China Identify other TDVAX markets to target Install and implement single use bio-reactor plant, increasing the capacity for future products Develop and install small scale microbial fermentation capability, increasing the capacity for future products Install and implement small to intermediate scale cGMP oligonucleotide plant, increasing the capacity for future products

UMMS scientific harmonization team executes first UMMS program requiring incremental capability Engage with industry, governments and non-government organizations (e.g. WHO, PAHO, MSF, GAVI and IAVI) for expanded access to S315 (huDAT) for distribution and monitoring Execute Canadian regulatory strategy Develop regulatory strategy for China Investigate feasibility of other identified markets


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NOTES

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STRATEGIC

GOAL

EDUCATION & TRAINING

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To strengthen MassBiologics’ role in education and training of UMMS learners, faculty and staff in the drug development process, develop the skillsets necessary to be successful in employing the most promising contemporary platforms for discovery, development and manufacture of advanced therapeutics. Our research enterprise is committed, in spirit and in action, to pursuing science that matters and makes a difference in the lives of patients and populations. While priming the engine of discovery is absolutely essential, scientific discoveries alone will not effectuate the impact we intend to make through our research efforts. In order to advance human health, we must align and

IN COLLABORATION with the UMMS Office of Diversity and Inclusion, MassBiologics will prioritize reaffirmation of its efforts to build a robust pipeline of future workers for MassBiologics and the Commonwealth of Massachusetts. Harmonization with the medical school also includes tapping into the knowledge and expertise of UMMSglobal health researchers to enhance uptake of developed products across the globe, and measure and communicate their impact. MassBiologics is a unique asset for research and education in applied science, translational medicine, and biotechnology in the broadest, real world sense: from bench to bedside. Enhancing existing partnerships between MassBiologics and

integrate our complementary expertise across the research continuum, from basic science to translational research through to regulatory science and outcomes research. Creating a predictable and repeatable research and development process will provide us with key insights, data and evidence, all of which are required to advance the science of translation.

UMMS will facilitate integrated faculty development, graduate and postdoctoral pathways and optimal utilization of the MassBiologics applied science knowledge, experience and infrastructure. In the coming years, we will ensure that we are responding to the educational and development needs of our faculty and employees. We will enhance existing partnerships with the UMMS Center for Biomedical Career Development to provide education to students regarding technical industry roles. We will develop tailored pathways for MassBiologics faculty to develop and advance within their respective academic areas. Tailored pathways of study that engage the commercial biologics ecosystem as partners in the educational experience will characterize our

approach to workforce development. Entrepreneurship and leadership skills will be prioritized in our new programs of self-directed learning along with specific competencies in regulatory science. We will strengthen and broaden existing MassBiologics workforce development programs to create a pipeline of trained scientists and managers for the biologic manufacturing ecosystem. MassBiologics will enhance existing programs to provide hands-on relevant mentoring and experience in the applied skills necessary for translational medicine striving to create the next Medicines for Better Lives. Local high school interns, undergraduate interns, graduate students, medical students and postdoctoral candidates will be trained


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across all of the technical disciplines required to discover, develop and manufacture the newest biologic medicines. These trainees will create a pipeline of highly competent candidates for MassBiologics as well as the biologic medicine ecosystem of the Commonwealth of Massachusetts. A highly trained

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Major Milestones

workforce will help continue the dominance of the region in biologic medicines. We will continue to expand the local programs for high schools, community colleges and local four-year colleges. Community engagement in workforce development will be emphasized.

Partnerships with local high schools, community colleges and UMass campuses will be enhanced and formalized in order to create a pipeline of trainees capable of advancing the translation of biologic discoveries into commercial products.

We have established the following major milestones to guide the first year of our Education & Training strategic goal.

Establish steering committee of UMMS, MassBiologics and other UMass stakeholders Define program goals and pathways of career development Develop and implement curricula and rotations for UMMS students and MassBiologics workforce Apply for training grants

Consider development of certificate/diploma programs Initiate training program for UMMS students and MassBiologics workforce Develop and implement outreach events (e.g., on-site boot camp introduction to drug development)


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STRATEGIC

GOAL

OPERATIONAL EXCELLENCE & FINANCIAL STEWARDSHIP

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Establish models for outstanding translational research support services, vibrant working environments and highly efficient infrastructure. MassBiologics’ efforts will include close alignment with the Medical School, from education, business development and novel medicine introduction. Alignment with UMMS and specialized centers of excellence, highlighted by UMMS Bridge and the Office of Advancement, will be integral to our goal of reaching a new level of operational excellence in the years ahead.

Emphasis will be placed on expanding markets in which TDVAX is distributed and establishing a more robust front door for contract development and manufacturing services for viral vaccines, protein-based therapeutics (including antibodies, vaccines and gene editing therapeutics), gene therapies and oligonucleotides.


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For the next five years, our specific priorities to realize our strategic direction in operational excellence and financial stewardship include the following: Enhance MassBiologics’ marketing and sales capabilities to increase the utilization of contract development and manufacturing organization infrastructure for MAbs, vaccines, gene therapies and nucleic acid synthesis. By investing in new strategies for broadening MassBiologics’ marketing and sales capabilities, additional programs for existing capabilities in MAbs and vaccine manufacturing, and gene therapies will be introduced into the various MassBiologics manufacturing plants. This will better utilize existing capacity and maximize revenues. The introduction of new capabilities in nucleic acid synthesis and microbial fermentation for manufacture of gene-editing reagents will more efficiently utilize our facilities creating additional revenue opportunities without adding overhead costs.

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Major Milestones

Invest in quality control and process development infrastructure to allow more contract development work to be undertaken. The cGMP manufacturing capacity of the various MassBiologics plants in every case is greater than the capacity of the process development and quality organizations. This results in complex scheduling challenges requiring very specific mixes of programs further constraining the ability to accept revenue generating programs. Investment in infrastructure, including personnel, equipment and automation, will enhance the ability to recognize revenue from all segments of the therapeutics market supported by MassBiologics. Implement cost savings process improvements and increased volume to improve impact from TDVAX sales. Through implementation of cost savings programs such as

automated visual inspection and closed compositing into the TDVAX manufacturing process MassBiologics will maximize the impact of TDVAX sales. Expand Reagent Products. Growing the NIH funded Nonhuman Primate Reagent Resource, a unique unit of MassBiologics, will more efficiently utilize MassBiologics’ nonclinical manufacturing capacity. In addition, there are opportunities to commercialize tetanus and diphtheria in the reagents market and introduce tetanus and diphtheria toxoid into the reagent market both in cGMP and reagent versions. We will further investigate the commercial potential of existing and future MassBiologics discoveries for applications beyond human use, such as laboratory reagents, veterinary medicines, and diagnostic and industrial applications

We have established the following major milestones to guide the first year of our Operational Excellence & Financial Stewardship strategic goal.

Add two process development and two quality control resources

Implement improved closed compositing process

Initiate market assessment for Nonhuman Primate Reagent resource and create phased approach to expanding capabilities and production

Secure commercial manufacturing contract for gene therapy product

Establish a working group to catalogue our library and pipeline for potential markets other than human medicines

Develop a partnership for marketing gene and cell therapy development and manufacturing services

i. Implement phased approach for expansion of Nonhuman Primate Reagent Resource

Manufacture biologics and gene therapy products for clients

ii. Rank the library and pipeline according to potential markets other than human medicines and implement research to define the market potential of the top candidates or categories of products

Manufacture fermentation-based products for clients

Commercialize tetanus toxoid reagent

Manufacture oligonucleotides for clients Initiate project plan of next TDVAX quality/manufacturing improvement (closed aliquoting, purification operations at room temperature.)

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M ASSBIOLOGICS STR ATEGIC PL AN IMPAC T 2025

NOTES


University of Massachusetts Medical School Michael F. Collins, MD, FACP Senior Vice President for the Health Sciences, University of Massachusetts Chancellor, UMass Medical School

Terence R. Flotte, MD Executive Deputy Chancellor, Provost and Dean, School of Medicine

Senior leadership of MassBiologics Mark S. Klempner, MD Executive Vice Chancellor, MassBiologics Professor of Medicine Rebecca Cannon, PhD Deputy Director, Quality Assistant Professor of Medicine Frank Fazio, MS, MBA Deputy Director, Operations and Innovation Research Professor, Chemical Engineering at UMass Lowell Shekar Ganesa, PhD Senior Director, Process Development Assistant Professor of Medicine

IMPACT 2025

Group Leaders:

Christine Kelberman, MBA Controller Eric Peterson Deputy Director, Manufacturing and Facilities John Sullivan-Bolyai, MD Deputy Director, Clinical and Regulatory Affairs Associate Professor of Medicine Yang Wang, MD, PhD Deputy Director, Product Discovery Associate Professor of Medicine

Discovery & Translational/Clinical Research Yang Wang, MD, PhD, Shekar Ganesa, PhD Global Impact John Sullivan-Bolyai, MD, Eric Peterson Education and Training Yang Wang, MD, PhD, John Sullivan-Bolyai, MD Operational Excellence and Financial Stewardship Christine Kelberman, MBA, Rebecca Cannon, PhD


M A S S B I O L O G I C S S T R AT E G I C P L A N

MOVING FORWARD

u m a s s m e d .e d u /m a s s b i o l o g i c s /

MassBiologics 460 Walk Hill Street Mattapan, MA 02026 (617) 474-3000 information @ massbiologics.org


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