10 Most Innovative Regenerative Medicine Companies in 2022 by insightscare

January Issue 01 2022

MOST

Innovative

Regenerative

Medevolve The Application of Stem Cell Therapy

Medicine

Companies in 2022

A New Dawn Could Regenerative Medicine Be the Key to Treating Malignant Diseases?

Laura Bosworth CEO, and Founder

TeVido BioDevices

Recuperating Lost Skin Pigmentation Through Advanced Cellular Therapy

A Paradigm Swing in the Healthcare Niche

egenerative medicine is an interdisciplinary ﬁeld that connects engineering and life science principles to promote regeneration and can conceivably restore diseased and injured tissues and organs. Regenerative medicine encompasses numerous strategies, including materials and newly generated cells and various combinations, to take the place of missing tissue, eﬀectively replace it structurally and functionally, or contribute to tissue healing. The body's innate healing response may also be leveraged to promote regeneration, although adult humans possess a limited regenerative capacity than lower vertebrates. Organ and Tissue loss through disease and injury motivates the development of therapies that can regenerate tissues and reliance on transplantations.

Since tissue engineering and regenerative medicine emerged as an industry about two decades ago, several therapies have received Food and Drug Administration (FDA) clearance or approval and are commercially available. If compared with this scenario, medical devices, a vast category that includes noncellular products, such as acellular matrices, generally reach the market after only three to seven years of development and may undergo an expedited process if they are similar to these preexisting devices. Scientiﬁc and clinical progress has enabled the present era of gene therapy and cell therapy on multiple fronts. Acellular products may be preferable from a regulatory and

development perspective, compared with cell-based products, due to the less arduous approval process. On the brighter side, increased accuracy of disease models may improve the eﬃcacy of regenerative medicine strategies and enhance the translation to the clinic with favourable approaches. Focused on the exponential industry sagacity and fundamentals, Insights Care brings you its edition of the '10 Most Innovative Regenerative Medicine Companies in 2022', embracing the journey of these companies with the profound expertise that is enabling innovations in the healthcare niche. Have a good time reading!

Anish Miller

Editor’s Note

BioRestorative Therapies Ushering in An Era of Innovations in Regenerative Medicine

RepliCel Life Sciences, Inc. Holostem Terapie Avanzate

Enhancing Human Body through Regenerative Medicines

Leading the Revolution in the Regenerative Medicine Space

24 CXO Highly Accurate, Minimally Invasive Test Meets Demands for Early, De nitive Diagnosis of Alzheimer’s Providing with a Heart Disease,Reduces Economic Burden that Cares - Frank Amato

Cover Story

Recuperating Lost Skin Pigmentation Through Advanced Cellular Therapy

08 20

Articles

Medevolve

A New Dawn

The Application of Stem Cell Therapy

Could Regenerative Medicine Be the Key to Treating Malignant Diseases?

C O N T E N T S

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Most Innovative

Regenerative

Medicine Companies in 2022

Company Name

Featuring

Description

BioAesthetics

Nicholas Pashos, Founder

BioAesthetics’ mission is to transform lives through advancement in biomaterials.

BioRestorative Therapies

Lance Alstodt, Chairman and CEO

BioRestorative Therapies is committed to developing stem cell therapies to address unmet needs in patients with highly prevalent conditions.

Celixir

Ajan Reginald, CEO

Celixir is devoted to discovering breakthrough medicines that change the standard of medical care for patients.

Exopharm

Aislinn Treloar, CEO

Exopharm is a clinical-stage biopharmaceutical company at the forefront of transformative medicines using exosomes or extracellular vesicles (EVs) and is pursuing a pipeline-driven platform strategy.

Holostem Terapie Avanzate

Marco Dieci, CEO

Holostem is the ﬁrst biotechnological company entirely devoted to development, manufacture, registration and distribution of Advanced Therapies Medicinal Products (ATMPs) based on cultures of epithelial stem cells both for cell and gene therapy.

Kadimaste

Asaf Shiloni, CEO

Kadimastem is a clinical stage biotechnology company, with a unique platform for cell therapy that enables the production of oﬀ-the-shelf cell-based products for the treatment of unmet medical needs.

Neurona Therapeutics

Cory R. Nicholas, CEO

Neurona Therapeutics is a clinical stage biotechnology company focused on the discovery and development of cellbased therapies to treat intractable neurological disease.

RepliCel Life Sciences

Lee Buckler, CEO

RepliCel is a regenerative medicine company developing autologous cell therapies to treat conditions linked to a deﬁcit of healthy cells required for normal healing and function.

SYNAPS Dx

Frank Amato, CEO

SYNAPS Dx is the exclusive licensee of the worldwide patent portfolio covering the biomarker technology.

TeVido BioDevices Inc

Laura Bosworth, Founder and CEO

TeVido's vision is to change the current approach to reconstructive surgery starting with the loss of skin color caused by disease or scarring.

Cover Story

Laura Bosworth CEO, and Founder

Recuperating Lost Skin Pigmentation Through Advanced Cellular Therapy

TeVido supplies the cell processing expertise, and the clinic focuses on what they know. This procedure is largely performed by dermatologists or plastic surgeons

10 Most Innova ve Regenera ve Medicine Companies in 2022

egenerative medicine—the ﬁeld of medicine that repairs or replaces damaged tissues or organs—is among the most cutting-edge sectors of medical innovation today. Using a patient’s own skin is one of the most common forms of regenerative medicine. TeVido BioDevices is one of the prominent names among the new age companies that provide these advance regenerative procedures. TeVido’s vision is to change how reconstructive surgery is done. Founded in the year 2011, the company is spearheaded by its Founder and CEO, Laura Bosworth, a former Fortune 50 exec with 30+ years of cross-functional industry experience. In the following extract, we explore how the company has been driving change in the regenerative medicine arena with its cutting-edge manufacturing techniques that are combined with advances in the cellular therapy to restore lost pigmentation in the skin.

Skin transplants, or grafts, were initially described 25003000 years ago(1). The procedure moves a piece of skin from one part of a patient’s body to another (known as an autologous transplant). During the Middle Ages, the techniques were largely lost. However, by the mid-late 1800s, they were back, and many of these techniques, with some modiﬁcations, are still used today.

The epidermis is made up of several cell types. About 90% are keratinocytes that make up most of the skin structure. Melanocytes are located at the dermalepidermal junction, typically 3-5% of epidermal cells. Melanocytes produce the pigment melanin, which they can then transfer to other epidermal cells. Melanin can be yellow, brown, or black in color, and the more of it that is produced by melanocytes, the darker is the skin.

Since the 1990s, one such modification - transplanting epidermal cells - has been successfully performed on thousands of patients. Yet this technique is only used by a small number of research facilities around the world due to the cost, complexity, and regulatory requirements of preparing the cells. It requires a considerable amount of expertise and does not fit into the clinical workflow of a busy dermatology or plastic surgery practice.

natural color (pigment) due to scarring or skin conditions, such as vitiligo. Loss of skin color is difficult to treat, and available solutions are not clinically effective. However, 25 years of academic research show epidermal skin cell transplants are both safe and effective(2). Very few doctors can offer this choice, until now, with TeVido’s TruPigment™.

Epidermal cell transplants – clinical history

“Innovation comes in many ﬂavors,” said Laura Bosworth, TeVido CEO, “ours is about simplifying a clinical procedure to make it easy to access.” She goes on to explain, “Skin cell transplants are a known surgical option for skin color regeneration. Yet, they are underutilized due to the challenges of processing the living cells for transplantation. TeVido BioDevices is making these lifechanging skin cell transplants available to doctors and the patients who need them.” TeVido leverages the regenerative power of a patient’s own body to repair and restore lost skin color. Skin can lose its

What causes loss of skin color? Vitiligo (vit-ih-LIE-go) is a disﬁguring disorder that causes loss of skin color resulting in scattered white patches. It is due to an absence of functional pigment cells (melanocytes) in the aﬀected area. About 1% of the world's population has vitiligo, with an estimated 2-5 million in the U.S. It can be emotionally devastating, and there is no cure. The aim of vitiligo treatment(s) is to reduce the contrast in color, but the most prevalent methods are highly variable, and when stopped, loss of skin color often returns. Up to

Innovation comes in many ﬂavors; ours is about simplifying a clinical procedure to make it easy to access.

70% of patients are dissatisﬁed with their treatment results. Skin cell transplants are most suitable for those with stable vitiligo. Depigmented (white/pale) scarring is a common complication of deep dermal wounds, including burns, caused by traumatic injury and surgery (3,4). In the U.S., this results in about 80 million new scars per year. Partial to full loss of normal skin color occurs in 15-25% of scars. Many techniques, such as phototherapy, dermabrasion, chemical peels, micro-needling, ablative laser resurfacing, and tattoos, have all been used, none of which are recognized as consistently eﬀective. Improving the appearance of hypopigmented scars has remained a clinical challenge with no current gold standard(5). A few other examples of skin conditions with loss of skin color are: • Halo Nevi: A mole that is surrounded by a depigmented ring or ‘halo’; Estimated at 1% of the population; found most commonly in children. The average age of onset is 15 years(6). • Nevus Depigmentosus: Commonly localized hypo melanosis that is seen in children, typically presents at birth, 0.5%-1.25% of neonates, or by three years(7); Est up to 3% of general population(8). • Idiopathic Guttate Hypomelanosis IGH: small (2-5mm) white spots(9,10) likely due to sun exposure, a very common condition to the point of being almost universal

in elderly fair-skinned individuals and most commonly a complaint of middle-aged (30’s) light-skinned women(10). Physical and Emotional scars Having an appearance that is different from ‘the norm’ can have a profound psychological impact on an individual. It can result in low self-esteem, depression, anxiety, difficulty interacting with others, and the ability to seek or keep a job. Severe disfigurement can truly be a disability when it affects the ability to lead a normal life (11). Not only is a person’s daily life affected, but they face emotional reactions to the trauma itself, including feelings of grief towards the loss of their former appearance. Some experience a profound disruption to the understanding of who they genuinely are as an individual(11). For example, Veterans with ‘appearance-related injuries’ – such as marks or scars on the head, stomach, neck, or arms - have higher rates of depression and report greater posttraumatic stress disorder (PTSD) symptom severity than those who were not injured or did not identify as having appearance-related injuries(12). According to the RAND Corporation (13), almost 20% of the veterans who served in either Iraq or Afghanistan, suffer from major depression or post-traumatic stress disorder. This applies beyond the military to the general population. TeVido’s TruPigment™ The creation of a centralized, scalable facility to prepare the cells for transplantation allows patients easy access to a surgical option for pigment regeneration. TeVido supplies the cell processing expertise, and the clinic focuses on what they know. This procedure is largely performed by dermatologists or plastic surgeons. The patient will have two simple procedures that are scheduled a day apart. On the first day, the physician takes a ‘paper-thin’ sample of healthy skin and ships that to TeVido overnight. This is very similar to a shave biopsy. Generally, the sample of skin is about 1/5th the size of the area to receive the transplant. TeVido provides all the shipping materials and arranges the pickup to make it easy for the clinic.

At TeVido’s facility, the sample is processed following FDA guidelines under Title 21 Code of Federal Regulations (CFR) Part 1271 for Human Cell and Tissue Products (HCTPs). Here the cells are isolated and suspended in neutral media (liquid). This is known as a non-cultured epidermal suspension (NCES). TruPigment™—TeVido’s NCES—is intended for homologous, autologous use. In other words, it is only used on the person who provides the sample.

Creation of a centralized, scalable facility to prepare the cells for transplantation allows patients easy access to a surgical option for pigment regeneration.

Quality control tests ensure each patient's cell suspension meets safety requirements and cell viability. TruPigment™ is packed and shipped back to the clinic. On the third day – the patient’s second appointment – the physician will prepare the depigmented area to receive the transplant. The very top layer of skin, the epidermis, is removed with a common procedure used in cosmetic and reconstructive surgery, laser resurfacing. This technique is commonly used to improve wrinkles or scars.

aesthetic clinics. This strategy has allowed TeVido to bring in revenue while continuing to work with early adopters of TruPigment™. The upcoming year will see TeVido ramp up activities with early adopters and build up the sales force. A Dynamic Leader

After the site is prepared, TruPigment™ is applied topically. The site is bandaged until cells are grafted, and the site has healed, which happens in 3-7 days. With successful engraftment, the healthy melanocytes begin to produce pigmentation, and over the course of about six months, skin color begins to return. As with laser resurfacing, the patient may have redness and swelling during the healing period. The risks for these procedures are low but include possible scarring, infection, and color mismatch. Results vary between patients, and a pigment transplant may not work for everyone. To see the best possible results, your doctor may recommend additional treatments such as the use of topical medications, light therapy, or additional surgical procedures. Looking ahead to 2022 In the Fall of 2019, TruPigment™ was transplanted to a handful of patients. Working closely with a local vitiligo specialist, TeVido was looking forward to seeing initial results when COVID-19 hit. All elective procedures went on hold, and the future was uncertain. With skills, equipment, and expertise in quality processes – TeVido quickly adapted and oﬀered Boutique COVID-19 diagnostic testing to international travelers and local

With a B.S. in Engineering, Ms. Bosworth started her career in manufacturing process development and quickly moved into management. She honed her product development skills leading custom software projects that included the creation and execution of multiple technical sales support functions, enabling over $500M in sales. She was frequently recognized for her contributions to sales, and her ability to understand customer pain points led her to leadership roles in product marketing. She launched several new business start-ups, such as professional services, within a larger corporation and has expertise in customer support services. Using her crossfunctional and international experience, she developed corporate-wide quality strategies that reduced operating costs and improved customer satisfaction. After 20 years in high-tech, Ms. Bosworth developed curricula, taught, and provided mentorship with several applied entrepreneurship programs, focused on mentoring aspiring underrepresented and women entrepreneurs to develop their own high growth companies. She co-founded a Women’s Entrepreneurship Accelerator and led a task force to create a culture of innovation at U.T. El Paso, where she served on the College of Engineering Advisory Board. In 2013 she received a Golden Nugget Distinguished Alumni Award from UTEP.

In 2011, she founded TeVido, initially based on UTEP technology. She successfully led the company through a product pivot that lowered time and cost to market, resulting in a commercially available product, TruPigment™, in the Fall of 2019. The company has received grants from the National Science Foundation, the National Cancer Institute, and the LIVESTRONG Foundation and is currently privately funded. Bequeathing the Keys to Excellence We asked Laura, what advice she’d give to those venturing into the discipline and business of Regenerative Medicine, to which she said, “There are core skills that translate across companies and industries. After 20 years in high tech, I was passionate about my move into a field where I can improve people’s daily life. But I found many people in the healthcare industry to be skeptical that such a move was possible. That was confusing to me. Every new role I took in “Corporate America” was a complete shift from what I had done before.” “I developed manufacturing processes and then moved to software development for semiconductor chip design. I had no software experience or chip design experience! I then moved into a role working directly with customers who were deploying new IT infrastructure. I had never worked with customers and knew little about IT systems. This is what can be great about working in “Corporate America.” “Big companies have a vast diversity of roles, and they are willing to mentor promising individuals. They are looking for people who can get things done. Many companies deliberately move these people across functions to develop a broad experience base in the leadership “pool”. These experiences are transferable – even across industry. Guess what? The level of complexity of semiconductor manufacturing is similar to that found in GMP standards for medical devices. Selling into a hospital is difficult and takes a long time. So is selling into a Fortune 500 company and selling into the automotive industry is different than selling into a retail company.” “You are always learning something specific – but there are a great many skills that will help you transition from role to role and pick things up quickly. What doesn’t transition is relationships. If your experience is selling into FORD and you want to become a salesperson in cardiology – that’s going to be hard! Unless, you have another way in. So, if you want to maximize your career flexibility try to have a

Causes of Scars (U.S.) More than 52,000 injuries have resulted from the wars in Iraq and Afghanistan(14), leaving physical and emotional scars for many. In the U.S., nearly 500,000 burns are treated each year by medical professionals; roughly half are children(15). 2 million people suﬀer with severe acne scarring There are over 43 million surgeries performed anually(16) – all of which can lead to scars from the trauma itself or the required surgery.

variety of roles and know how to make things happen in each. Figuring it out and getting it done is what will pay oﬀ.” Recent Awards and Recognition • October 2020 – TeVido BioDevices was one of six companies invited to present at the 2020 Fall Clinical Dermatology Conference to a panel of expert judges and audience members at the Skin Health Innovation Competition. This is a chance for attendees to learn about emerging solutions in clinical dermatology and aesthetic medicine. • January 2020 – TeVido BioDevices was one of ﬁve startups selected to present at the Inaugural Aesthetics Technology Summit (ATS) in Southern California. ATS brings together leading physicians, industry, and innovators to discuss ground-breaking medical aesthetic technologies as well as unmet clinical needs and new business opportunities. • September 2019 - TeVido BioDevices Announces Availability of TruPigment™ for use in restoring lost skin color.

TeVido clean room for TruPigment processing

Bibliography 1. Skin Gra ing: History of the Procedure, Indications, Relevant Anatomy. Available at: https://emedicine.medscape.com/article/1129479-overview. (Accessed: 26th October 2021) 2. Gupta, S., Narang, T., Olsson, M. J. & Ortonne, J. P. Surgical Management of Vitiligo and Other Leukodermas: Evidence-Based Practice Guidelines. in Surgical Management of Vitiligo (eds. Gupta, S., Olsson, M., Kanwar, A. J. & Ortonne, J.) 69–79 (Blackwell Publishing Ltd, 2007). doi:10.1002/9780470987568.ch9 3. Sterling, J. P., Heimbach, D. M. & Gibran, N. S. 15 Management of the Burn Wound. (2010). doi:10.2310/7800.S07C15 4. Mulekar, S. V., Issa, A. Al & Eisa, A. Al. Treatment of post-burn leucoderma with non-cultured melanocyte-keratinocyte transplantation (MKTP). Burns 37, 448–452 (2011). 5. Siadat, A. H. et al. Repigmentation of Hypopigmented Scars Using Combination of Fractionated Carbon Dioxide Laser with Topical Latanoprost Vs. Fractionated Carbon Dioxide Laser Alone. Indian J. Dermatol. 60, 364–8 (2015).

6. Zabawski, E. J. et al. Halo Nevus: Background, Pathophysiology, Epidemiology. Medscape (2016). Available at: https://emedicine.medscape.com/article/1057446-overview#a6. (Accessed: 17th April 2018) 7. Rashighim Mehdi MD & Burgin Susan MD. Nevus depigmentosus. VisualDX (2017). Available at: https://www.visualdx.com/visualdx/diagnosis/nevus depigmentosus?diagnosisId=52028&moduleId=101. (Accessed: 17th April 2018) 8. Achromic Nevus. DoveMed (2015). Available at: https://www.dovemed.com/diseases-conditions/achromic-nevus/. (Accessed: 17th April 2018) 9. Falabella, R. et al. On the pathogenesis of idiopathic guttate hypomelanosis. J. Am. Acad. Dermatol. 16, 35–44 (1987). 10. Gorman, Christopher R, M. & et al. Idiopathic Guttate Hypomelanosis: Background, Pathophysiology, Epidemiology. Medscape (2017). Available at: https://emedicine.medscape.com/article/1068422-overview#a4. (Accessed: 17th April 2018) 11. Harcourt, Diana; Rumsey, N. Psychology and visible diﬀerence | The Psychologist. Br. Psychol. Soc. 21, 486–489 (2008). 12. Tanielian, T. et al. Invisible Wounds: Mental Health and Cognitive Care Needs of America’s Returning Veterans. RAND Corporation (RAND Corporation, 2008). doi:10.2307/3522054 13. Weaver, T. L., Walter, K. H., Chard, K. M. & Bosch, J. Residual Injury, Appearance-Related Concerns, Symptoms of Post-Traumatic Stress Disorder, and Depression Within a Treatment-Seeking Veteran Sample. Mil. Med. 179, 1067–1071 (2014). 14. Fischer, H. A Guide to U.S. Military Casualty Statistics: Operation Freedom’s Sentinel, Operation Inherent Resolve, Operation New Dawn, Operation Iraqi Freedom, and Operation Enduring Freedom. (2015). 15. Burn Incidence and Treatment in the United States:2016. American Burn Association Available at: http://www.ameriburn.org/resources_factsheet.php. (Accessed: 18th July 2015) 16. Crandall, M. A. Wound Care Markets Vol. III Surgical and Trauma Wounds. III, (2009).

10 Most Innovative Regenerative Medicine Companies in 2022

Ushering in An Era of Innovations in Regenerative Medicine

tem cell technology has been a prominent topic since its introduction. In recent years, the advancement in stem cell therapy has reached a promising level. This advancement has brought great possibilities into light. Researchers are now working on finding ways to extend this therapeutic strategy to prevalent chronic ailments such as neurodegenerative diseases, diabetes, and heart disease. The ability of stem cells to self-renew and give rise to successive regenerations with varying degrees of differentiation capacity opens up a myriad of possibilities around creating tissues that might potentially replace diseased and damaged parts of the body with minimal danger of rejection and negative effects. According to a recent study, noncommunicable diseases account for six of the top seven causes of death worldwide. Regenerative medicine may be our best hope against such ailments. Patients are looking forward to these new innovations and BioRestorative Therapies is engaged in the arena by developing therapeutic products using cell and tissue protocols, primarily involving adult stem cells. In the following interview, Lance Alstodt, the Chairman and CEO of BioRestorative Therapies, sheds light on the company’s journey, its role in cell-based treatments, and the future of regenerative medicine.

Please brief our audience about BioRestorative Therapies, its USPs, and its role in the regenerative medicine space. We are a growing cell-based therapeutics development company in the field of regenerative medicine. We have two platform technologies. Our lead clinical program is BRTX100, an engineered stem cell for treating chronic lumbar disc disease, which is cleared by the FDA for a Phase 2 clinical trial, and our ThermoStem program, which uses cell-based therapeutics to target and address metabolic disorders, such as Type 2 diabetes, obesity, COVID-related ARDS and hypertension. In November 2021, we completed a financial restructuring pursuant to which we eliminated all debt, raised $23 million of capital, enhanced our governance and leadership and uplisted to the NASDAQ Capital Market. We are now on the precipice of initiating our Phase 2 clinical trial as well as accelerating the development of our secondary programs. Our lead clinical product, BRTX-100, is novel and highly differentiated relative to other cell-based therapeutics targeting disc disorders. Based on our differentiated approach and our history of treating patients with no safety concerns and strong outcomes, we are confident and optimistic that our FDA Phase 2 clinical trial will also yield such significant positive clinical outcomes.

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Lance Alstodt

Chairman and CEO

We are a growing cell-based therapeutics development company in the field of regenerative medicine.

About the Leader Lance Alstodt began his journey in the healthcare industry as an investment banker at JP Morgan, Bank of America Merrill Lynch (BAML) and Leerink Partners, advising on some of the largest and most significant transactions in the life sciences sector. A disproportionate amount of his time was spent in Orthopedics and specifically within the Spine sector. Helping to create and shape a multi-billion-dollar industry through equity and debt related financings and M&A activity, he has had the good fortune of working with and advising Medtronic, Nuvasive, Globus, J&J, Zimmer, Stryker, Biomet, Mazor Robotics, Alphatec, Seaspine, and many other emerging growth companies that have been

acquired by the large strategic players in the sector or financed to become larger independent companies. Mr Alstodt founded Medvest Capital, a healthcare fund that invests primarily across the healthcare spectrum, from healthcare services to biopharma. The fund has grown organically and, through domain expertise, he has been able to assist many of the companies within the fund with operating, regulatory and financial issues. His leadership at BioRestorative is a natural fit, given the challenges that the company has faced and the opportunities that are now in front of it.

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What other solutions and services does BioRestorative Therapies offer that gives it an edge over its competitors? We don’t have a one-size-fits-all cell-based therapeutics to treat everything. Our programs are targeted for particular indications that take advantage of the various therapeutic properties of different cell types. For example, in chronic lumbar disc disease, the disc is highly compromised and has a cellular environment that isn’t receptive to cell-based intervention. In particular, the oxygen content is very low due to minimal blood flow. BRTX-100 are stem cells that are manufactured in a low oxygen environment to enrich the cells that will survive this difficult environment. Providing enhanced cell survivability will enable the cells to provide optimal therapeutic benefits and potentially result in better clinical outcomes than what others have been able to realize. What is your opinion on the impact of the current pandemic on the global healthcare sector, and what challenges did you face during the pandemic and subsequent lockdowns? The global pandemic has had a tremendous impact on the global healthcare sector and how healthcare is administered. What is truly amazing is seeing how the regulatory path to bring a novel product to market can be adjusted when the need arises. When there is a need, science always finds a way. At the very onset of the pandemic, BioRestorative, under previous management, filed for Chapter 11 protection and faced the possibility of liquidation and closure. Between March and November 2020, Lance Alstodt and Francisco Silva restructured the entire company, settled all outstanding creditor claims and preserved the publicly traded entity. The company demonstrated tremendous resolve and execution expertise in order to emerge from Chapter 11 in November 2020 and raised capital all while advancing and continuing to develop its technology and intellectual property, the cornerstone of the company today. With constant development in medical technologies, in your opinion, what could be the future of the regenerative medicine space? Regenerative medicine is advancing at such a fast pace. The combination of gene modification and cell-based therapeutics is providing groundbreaking treatment options for patients who otherwise had no options.

Specifically, within spine, many of the large spine centers across our country have initiated programs and teams dedicated to regenerative medicine. It is the future of spine and orthopedics among other applications. What would be your advice to the budding professionals aspiring to venture into the biotech industry? Having spearheaded BioRestorative’s emergence from Chapter 11, its $23 million capital raise and its uplist onto the Nasdaq Capital Market, I had a first-hand view of how a company with great science and technology was at the brink of closing because of some critical issues pertaining to capital structure and financing. It is critical that aspiring biotech professionals understand not only the scientific aspects of their programs and technologies but the mechanics and process behind capital markets within their sector and how best to leverage assets in order to fund clinical programs. How do you envision scaling BioRestorative Therapies’ operations and offerings in 2022? Since we now have $23 million on our balance sheet and are debt free, we are turning all our focus on initiating our Phase 2 clinical trial. We have already begun expanding our cGMP manufacturing facility and are looking to expand the number of employees we have in order to reach our goal of being first in man with BRTX-100 by mid-2022.

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Medevolve

The

Application of

Stem Cell Therapy

“

ell therapies are rapidly emerging as potentially curative, individualized treatments for many of the world's most challenging diseases."-Alain Vertes, Director of the EU section of the Alliance for Regenerative medicine and managing director of NxR Biotechnologies.

tissues and muscles. Stem cells originate from two main sources: adult body tissues and embryos. Generally, these stem cells lie dormant unless and until they are required to regenerate any damaged or lost tissue. Applications

Rightly quoted, the importance of the smallest unit, the cell, is phenomenal. Stem cells are the basic category of cells found in humans and animals which have the ability to divide and develop into cells with speciﬁc functions.

Scientists are also working on ways to develop stem cells from other cells, using genetic "reprogramming" techniques.

Stem cells can be considered as the basic raw resource from which other new cells with speciﬁc qualities can be generated. Under the right ecosystem in the human body or in a conducive lab environment, stem cells divide into newer cells, also termed daughter cells.

Stem cell therapy has numerous applications in the treatment of certain diseases and complex health disorders. There is extensive research being conducted worldwide in leveraging their qualities to regenerate for customization of alternative and eﬀective cures.

Sources of stem cells

Stem cells are common everywhere in our body, primarily found in our blood, bone marrow, brain, skin, heart, liver

Treatment of Ocular disorders The inability to complete recovery of visual function and complications that follow in the conventional

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treatments have shifted the search for a new form of therapy using stem cells. Stem cells play a major role in rebuilding the degenerated cells despite being present in low quantity and their state of dormancy in the body. Unlike other tissues and cells, regeneration of new optic cells responsible for visual function is rarely observed. Understanding the transcription factors and genes responsible for optic cells development will assist scientists in formulating a strategy to activate and direct stem cells renewal and diﬀerentiation. Stem cell-based therapy holds an extraordinary prospective in improving the lives of people who suﬀer from visual disorders. Research in this area will continue to grow to develop new remedies for treating and preventing the problem of vision loss. It carries a promising future in producing new biological elements used to treat vision loss. Ÿ

Blood ﬂow or the blood pressure gets altered due to the scar tissue formation when the heart tissue gets deprived of oxygen. The stem cells obtained from the bone marrow are used for repairing the damaged heart and blood vessels. Ÿ

Helping in Orthopedic treatments Patients experiencing who are experiencing discomfort because of various orthopaedic conditions, sportsrelated injuries, or spinal issues.

Control and treatment of auto-immune diseases For the patients living with conditions like lupus and rheumatoid arthritis, application of stem cell therapy for autoimmune diseases is a relatively newer option. In the autoimmune diseases where the immune system attacks its own organs, tissues, and cells, this therapy helps to minimize the downtime that the patients have to deal with and it being minimally invasive. This proves to be a big advantage for patients who do not opt for the surgery.

Stem Cell Therapy Applications in Clinical Research Advancements in stem cell therapy continue to shed light on how stem cells may be used in various clinical applications, which include cell replacement therapies, immunomodulatory therapies, etc.

Stem Cells Aiding the Treatment in Cardiovascular Diseases

Stem Cell Therapy in Fertility Treatments Ÿ

Stem cells are now increasingly being tested as promising alternative therapies in translational research of regenerative medicine. Exciting progress has been made to understand the biology and function of stem cells. Looking at the minimum ethical concern with easy availability of resources, extensive research is being conducted. Induced Pluripotent Stem Cells or IPSC and Mesenchymal Stem Cells or MSC are researched for their potential application in reproductive medicine, especially in cases of infertility resulting from azoospermia and premature ovarian insuﬃciency. Evolutionary divergence observed in pluripotency among animals and humans requires caution when concluding the data obtained from murine models to safely apply them to clinical applications in humans. More clinical trials based on larger sample people need to be carried out to investigate the relevance of stem cell therapy, including its safety and eﬃcacy, in translational infertility medicine.

Healing complex Incisions and Wounds Various types of research in stem cell application have successfully led to the regeneration of the local cells, improving the growth of new healthy skin tissues, stimulating new hair development after some odd injuries, and enhancing collagen production. It has contributed to the rapid recovery in its function in substitution of the scar tissue with new healthy tissue.

The Journey Ahead… The research in stem cell applications is noticed to reach new levels of identifying cures to the otherwise tough options for the current therapies, which is a great relief. Though a lot more needs to be done, we can certainly hope for the fact that stem cell therapy will play an important pivotal role in transforming the recovery and control of multiple health disorders.

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10 Most Innovative Regenerative Medicine Companies in 2022

Holostem

Terapie Avanzate Leading the Revolution in the Regenerative Medicine Space

umans realized the capabilities and effects of medicinal intervention long before the term ‘Regenerative Medicine’ was coined. The evolution of medicine started with small but significant discoveries and techniques that still have an impact on the field today. Practises such as cleaning and debridement of wounds using vegetable and mineral combinations were commonplace then and are still used today as home remedies. Regenerative medicine has come a long way since then, with modern scientists and research foundations zeroing more on cell and gene therapy, realizing its exponential potential in regeneration. One such name in the regenerative medicine space, which is entirely devoted to the development, manufacturing, registration, and distribution of Advanced Therapies Medicinal Products (ATMPs) based on cultures of epithelial stem cells, both for cell and gene therapy is Holostem Terapie Avanzate. In the following interview, Marco Dieci, the CEO of Holostem, talks in detail about the revolutionary contribution of the firm to medicine since its inception.

Please brief our audience about your company, its USPs, and the aspects that make it a leading name in the regenerative medicine space. Holostem Terapie Avanzate is a university spin-oﬀ founded in 2008 through the proﬁtable union among Michele De Luca and Graziella Pellegrini, the University of Modena and Reggio Emilia and Chiesi Farmaceutici S.p.A. We have a highly experienced management team with sound know-how derived from a long tenure both in business administration and in academic research, successfully applied for many years in translational medicine.

field of epithelial stem cell biology aimed at clinical application in Regenerative Medicine and played a pivotal role in epithelial stem cellmediated cell and gene therapy. Besides their pioneering work on the use of human epidermal stem cell cultures in the life-saving treatment of massive full-thickness burns and in repigmentation of stable vitiligo and piebaldism, they were first in permanently regenerating a functional urethral epithelium – by means of cultured urethral stem cells – in patients suffering from posterior hypospadias and an oral epithelium

Holostem is the ﬁrst biotechnological company entirely devoted to the development, manufacture, registration, and distribution of Advanced Therapies Medicinal Products (ATMPs) based on cultures of epithelial stem cells both for cell and gene therapy. Our main aim is to promote epithelial stem cell-based regenerative medicine for patients with no alternative therapeutic solutions. Michele De Luca and Graziella Pellegrini are internationally recognized as leading scientists in the

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Ours ATMPs are not only products but also 360° services that we oﬀer to our clinical partners.

Marco Dieci CEO

About the Leader

– by means of cultured oral mucosa stem cells – in patients with defects of the gingival epithelium. They were first in establishing human autologous limbal stem cell culture aimed at corneal regeneration in patients with severe limbal stem cell deficiency due to massive thermic and chemical burn-dependent destruction of the cornea. This treatment led to the recovery of vision in hundreds of patients with poor or no alternative therapy. Thanks to the high experience in the field and to a GMP facility authorized

to manufacture ATMPs for commercial use and for clinical trials, the company focuses its research on three therapeutic areas: corneal burns, epidermolysis bullosa, and hypospadias. It also has an ATMP currently on the market: Holoclar®, the ﬁrst autologous stem cell-based drug approved in Europe in 2015. It is a tissueengineered therapy indicated for moderate to severe limbal stem cell deﬁciency caused by eye burns from physical or chemical agents and capable of restoring the eyesight of patients with severe cornea damage.

Marco Dieci began his career at Chiesi Pharmaceuticals, also collaborating in R&D of surfactant indicated in the prevention and treatment of prevention and treatment of respiratory distress syndrome in premature infants. He then spent over a decade as Director Industrial Operations at MolMed, following GMP development, both of all proprietary projects and those carried out for external customers. His last professional commitment was the design, implementation, and start-up of the Pharmaceutical Workshop of Ospedale Pediatrico Bambino Gesù in Rome. He has been managing Holostem since 2018.

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What other solutions and services do you offer that gives you a leading edge over its competitors? Ours ATMPs are not only products but also 360° services that we offer to our clinical partners. In fact, in addition to the manufacturing of our medicinal products, we offer dedicated training to medical staff who will apply the therapy. Moreover, we support each Physician being present with our Medical Service Team during every surgical phase and throughout the transplantation process and offer assistance both pre-and post-treatment. Our staff's deep and internationally recognized scientific background and the constant effort made in the research and development of our products represent an important strength of Holostem in the ATMps market. What is your opinion on the impact of the current pandemic on the global healthcare sector, and what challenges did you face during the pandemic and subsequent lockdowns? The COVID-19 pandemic has had a major impact in our field as well. Specifically, we have had to stop treatments with Holoclar because all non-essential surgical procedures have been suspended to provide the care necessary to deal with the virus. Obviously, all healthcare facilities have been reorganized to prioritize the emergency. In mid-2021, activities finally resumed, and so far, they seem to be going well, although still sporadically. Although the latest data on new pandemic waves in Europe, we hope that in the coming months, it will be better. With constant development in medical technologies, in your opinion, what could be the future of the regenerative medicine space?

We expect technology to streamline the manufacturing processes behind ATMPs, which are currently still labor-intensive. In addition, recent advances examples include achievements in stem cells knowledge, developments in the fields of cell and gene therapies, new vectors, nanoparticle technology, minimally invasive surgical tools, new biomaterials, research in silico for studying proteins or developing new drugs, and more. Thanks to all these new technologies, regenerative medicine will carve out an increasingly large slice of standard medical practice, and the goal is to address more and more unmet needs. In order to achieve this goal, some issues closely related to the use of advanced therapies must be addressed, first of all, the market access through different national health systems. As an established leader, what would be your advice to the budding professionals aspiring to venture into the biotech industry? I will answer taking inspiration from the words of Steve Jobs: "stay hungry, stay foolish," changing them in the following: stay foolish for science and use this to be a game-changer in life treating people.

pandemic, we were able to activate new centers and continue commercial activities to treat a higher number of patients in Italy and in Europe. The goals for the near future are to bring our product to the UK, increase further the number of clinical centers where patients can undergo treatment with Holoclar, and increase the number of countries in which we operate, which currently stands at 8 (Italy, UK, Germany, Austria, Belgium, Netherlands, Denmark, and the Czech Republic). Lots of people can be cured with Holoclar, but they still don't know this. Our mission is to inform them and let them cure. Share with us the awards and recognitions that you have received so far since inception. Over the years, we have received several awards and recognitions. The most noteworthy are: Ÿ Ÿ Ÿ

In the biotech sector, where new knowledge runs fast and technology pushes, even more, it is essential to remain curious, have passion for what you do, be ambitious, and be always ready to get involved to learn and challenge yourself.

Ÿ Ÿ Ÿ

How do you envision scaling your company's operations and oﬀerings in 2021? The year 2021 was marked by COVID19, but also by Brexit, which aﬀected our work in the UK. Despite the

Prix Galien Netherlands 2016 for Holoclar Prix Galien UK 2016 for Holoclar Award for innovation 2018 – ISSCR (Michele De Luca & Graziella Pellegrini) Black Pearl Award – Scientiﬁc Award EURORDIS 2018 (Michele De Luca & Tobias Hirsch) International Prize “Lombardia è ricerca” 2019 (Michele De Luca, Graziella Pellegrini & Tobias Hirsch) Louis-Jeantet Prize 2020 (Michele De Luca & Graziella Pellegrini) European Tech Women Award 2020 (Graziella Pellegrini) ERC Advanced Grant 2021 (Michele De Luca)

Our researchers were also received by the president of the Italian Republic, Sergio Mattarella, in 2018.

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Highly Accurate, Minimally Invasive

Test Meets Demands for Early,

Definitive Diagnosis of Alzheimer’s Disease, Reduces Economic Burden - by Frank Amato, CEO and President, SYNAPS Dx

n estimated 5.8 million Americans age 65 and older are living with Alzheimer’s disease (AD), with projections showing that by 2050 that number will reach 12.7 million. Although AD is the most common type of dementia, there are many other kinds, including Lewy body dementia, Huntington’s disease, and Creutzfeldt-Jakob disease. Given the cost and complexity of diagnosing AD, it’s no wonder researchers are striving to determine as many aspects of AD and other dementias as possible to find new treatments to prevent, halt or reverse disease progression. An early diagnosis of AD can help determine if the symptoms a patient is experiencing are truly due to AD or some other conditions that may be treatable. Unfortunately, when it comes to diagnostic tests for AD, considerable confusion has prevailed in the marketplace, often without clarity of the clinical importance of what is being measured. To avoid pitfalls, it’s important for stakeholders to understand that, while the progression and increased severity of symptoms support diagnosis, only autopsy findings provide a definitive method to diagnose AD. What’s more,

AD often co-develops with other age-related neurological disorders, such as Parkinson’s disease and strokes. Diagnosing patients with AD or mild cognitive impairment begins with the patient’s medical history, along with mental status tests and physical and neurological exams. Physicians may utilize additional diagnostic testing modalities to identify patients with AD, including amyloid PET, MRI, and CSF-based biomarker testing. In line with the current coverage environment, however, payers note several limitations of these modalities. The most promising breakthrough to date is the first accurate, minimally invasive test for the definitive diagnosis of AD versus other forms of dementia. This test assesses losses of activity of nerve cells in the brain and their ability to form networks and communicate, addressing several of the limitations that payers and healthcare providers identify in existing AD diagnostic tools. Understanding Alzheimer’s Disease AD is a type of dementia that affects memory, thinking and behavior. AD accounts for 60-80% of dementia cases and is not a normal aspect of aging.

Scientists believe AD prevents parts of a brain cell from running properly. As damage spreads, nerve cells lose their ability to function, communicate, and eventually die, causing irreversible changes in the brain. Loss of synapses, or the connectors through which nerves communicate, seems to be the strongest correlation to losses in mental abilities in people living with AD. The majority of people with AD are 65 and older, with symptoms growing worse over a number of years. In the early stages of AD, memory loss is mild but gradually individuals lose the ability to respond to their environment. Typically, AD patients live four to eight years after diagnosis but can live as long as 20 years, depending on other factors. Two abnormal structures called plaques and tangles can contribute to damaging and killing nerve cells. Plaques are deposits of a protein fragment called beta-amyloid that build up in the spaces between nerve cells. Tangles are twisted ﬁbers of another protein called tau that build up inside cells. While autopsy studies demonstrate that most people develop plaques and tangles as they age, individuals with AD typically develop far more of them in areas of memory

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before spreading to other regions. Most experts believe plaques and tangles play a role in blocking communication among nerve cells and disrupting processes that cells require. This destruction and death of nerve cells and their synaptic connections contributes to memory failure, personality changes, problems carrying out daily activities and other symptoms of AD. However, the understanding of how AD progresses is evolving. A recent study of centenarians found varying levels of plaque and tangles at autopsy, with no correlation to a reduction in mental functioning during life. This reinforces that while tangles and plaque may be present in brain tissue, they may not be the primary cause of AD. Mounting evidence suggests that memory failure, personality changes, problems carrying out daily activities and other symptoms of AD are caused by loss of activity of synapses and neurons. This reinforces the need to assess the activity and health of nerves in the brain and their synaptic connections when assessing losses to mental abilities associated with AD. Challenges in Addressing AD Memory loss can be brought on by a myriad of medical issues, including Lyme disease, vitamin deﬁciencies, thyroid issues, drug interactions and the various forms of dementia. Some of the conditions that are often mistaken for AD can easily be addressed with inexpensive interventions. Without a deﬁnitive diagnosis, however, it’s frustrating, expensive, and overwhelming for patients and families, providers, and payers to know how to proceed in the care journey. One-in-three patients with memory issues do not have AD disease and can

often get treatment that's more appropriate for a non-AD patient. For AD patients, it's well understood that no drug, including the one recently approved by the FDA—exclusively for patients who are early AD patients or in the very early stages of dementia—can treat the underlying disease. Other drugs provide only temporary symptomatic relief. An early diagnosis allows patients to start clinical interventions sooner, providing a cost savings for payers, as well as saving time, money, and the despair of not knowing for those involved. Early diagnosis also gives patients the chance to have a say in their own care.

patient’s disease and supporting their quality of life vs. treatment. Caretaker burden is also signiﬁcant. Once a disease-modifying therapy is available, it will be expensive and AD patients may require long-term therapy. Payers anticipate the cost of a diagnostic test to be relatively minor in comparison to disease-modifying drug therapy. The new AD test currently available on the market assesses the volume and activity of neurons and their synapses, loss of which are the main drivers of clinical AD. This test needs to be performed as part of the cognitive workup of the patient and may be a cost-eﬀective way to ensure appropriate use of expensive treatments.

Payer Challenges Value of Accurate AD Test Payers are primarily concerned about AD for their Medicare Advantage populations—a signiﬁcant population that is projected to increase. In terms of cost, sustainability is a key. Therefore, the faster an AD diagnosis can be made, the better. Payers perceive current diagnostic tools—amyloid PET scans, MRI scans, CSF-based testing—to be costly, without validity and potentially invasive. Few published coverage policies exist for diagnosis of AD. What’s more, emerging biomarkers (e.g., AB40, AB42, P-tau) are either not subject to formal polices (8/10 plans) or not covered (2/10 plans). This means that accurate and early diagnosis of AD, along with diseasemodifying treatments, are critical to meet payer needs. Given the aging population and potential for approval of expensive therapies in the future, payers are more primarily concerned with the future cost of AD than current costs. Cost drivers include maintenance of the

The three assays in this test have demonstrated >95% sensitivity and specificity for identifying AD, giving patients and families the answers that they need, enabling providers to make a conclusive diagnosis, and allowing payers to establish protocols and prior authorizations for prescribing and reimbursing treatment. It also helps pharmaceutical companies identify appropriate clinical trial participants. The AD test can be utilized as a tool to manage appropriate patient access to future approved therapies, in addition to the clinical and economic benefits of improved early, accurate diagnosis. The test identifies the AD-specific degeneration biomarker for a definitive diagnosis, differentiates AD from other non-AD dementias and identifies those with AD in addition to other degenerative pathologies. This is good news for every stakeholder, especially for patients and their families who are seeking answers and a path forward.

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A New Dawn

Regenerative Medicine Could

Be the

Key to Treating

Malignant Diseases? T “

he Regenerative medicine evolution is upon us. Like iron and steel to the industrial revolution, like the microchip to the tech revolution, stem cells will be the driving force for this next revolution." – Cade Hildreth, Entrepreneur, and former USA Rugby Player.

The insufficient results from the traditional therapies for malignant diseases like cancer treatment have led to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to curing cancer. Stem cells possess unique biological actions, including selfrenewal, directional migration, differentiation, and modulatory effects on other cells. These qualities can be utilised in regenerative medicine, therapeutic carriers, drug targeting, and the generation of immune cells. Regenerative medicine involving stem cell therapy covers stem cells and has provided hope in the fight against cancer.

It can improve the therapeutic eﬃcacy of other treatments due to its enhanced target on malignant tumours lowering the eﬀect on other areas.

Numerous stem cell strategies are investigated in clinical research and have shown promising development in cancer treatment. Catalytic Paradigm Shift Stem cells from different sources exhibit different proliferation, migration, and differentiation capacities, which determine their application in anti-tumour therapy. The hematopoietic stem cells or mature adult cells in the bone marrow are derived from cord blood. This is currently the single methodology of stem cells that the FDA approves to treat malignant diseases of multiple myeloma, leukaemia, and some kinds of blood system disorders.

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Mesenchymal stem cells possess unique biological properties and are widely used to support other therapies or deliver therapeutic agents in treating various cancers. Whereas the neural stem cells located in the central nervous system possess the ability to self-renew and generate new neurons and glial cells. In murine models, they are tested to treat primary and metastatic breast, lung, and prostate cancers. Epigenetic mutations in normal stem cells generate the cancer stem cells or immature parent versions of tumour cells. These cells are found within tumour tissues, playing an essential part in cancer growth, metastasis, and recurrence. So, targeting these cancer stem cells can provide a promising hope in treating various types of solid tumours.

Various strategies have been developed for cancer treatment using stem cell therapy, including HSC transplantation, MSC infusion for post-cancer treatment, stem cells for therapeutic carriers, generation of immune eﬀector cells, and vaccine production. HSC Transplantation method After rounds of high-dose radiotherapy or chemotherapy, the transplantation of hematopoietic stem cells is used as a standard procedure for treating multiple myeloma, leukaemia, and lymphomas. The methodology has recently been widely researched in preclinical and clinical trials, in conjunction with immunotherapy or chemotherapy, in treating various cancers such as breast cancer, sarcomas, neuroblastoma, and complex brain tumours.

Starting From The Bone Marrow MSC Transplantation method post-cancer treatments The hematopoietic stem cells are formed in the bone marrow. However, during the process of chemotherapy cycles, the blood-forming cells get extensively damaged as well. The patients are given intravenous injections of autologous hematopoietic stem cells in such situations. This initiates the returning of the cells leading to the rapid migration into specific stem cell pockets. Upon entering the bone marrow, the transplanted stem cells undergo settlement and become functional, promoting the growth of new special blood cells. Tumour Tropic Effect The tumour cell environment, where the extracellular matrix and secreted paracrine factors are deposited, defines tumour growth and invasion. This is done by attracting the unidirectional migration of various types of cells, for example, mesenchymal stem cells, endothelial cells and infiltrating immune cells. Tumours are considered chronic wound tissue with sustained hypoxia, inflammation, and oxidative stress events that cannot heal. Hence, the migration of cells toward the tumour microenvironment is supposed to be like their migration to injured or ischemic sites. Both tumour cells and tumour-associated immune cells can involve this process through the secretion of various chemically induced factors.

Chemotherapy and Radiation treatments of aggressive cancers involve invasive tumour removal and high-dose therapy leading to damage to normal tissues and the hematopoietic system. It has revealed that the infusion of mesenchymal stem cells helps maintain the undifferentiated state and proliferation of HSCs, thereby noticeably improving the output of the treatment. MSCs with immunomodulatory effects could effectively reduce strong immune responses in patients with refractory GVHD. Recent clinical trials have shown promising results with no adverse effects after the co-transplantation of MSCs and HSCs. MSCs are also found to facilitate the recovery of injured organs and enable body tolerance to high-dose chemotherapy to improve tumour-removing effects. A Ray of Hope Though the progress made in the clinical research of regenerative medicine has taken a giant leap in discovering possible cures, the research has a long way to go in the complete and effective treatment of malignant diseases. Still, it provides a ray of utmost hope.

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RepliCel Life Sciences, Inc. Enhancing Human Body through Regenerative Medicines

lants are given the special abilities to regrow their organs. Some animals, such as lizards, can regrow their tail. Talking about human beings, the liver is the only internal organ that can regenerate. But blessed with intelligence, we are inventing new technologies every day to achieve better health. The advancement of medical science has eased human life signiﬁcantly, and the next chapter is regenerative medicines. Regenerative medicine and tissue engineering have emerged as essential therapy options for a wide range of human disorders, with the goal of replacing, repairing, or improving the biological function of damaged tissues and organs. Though the research is in its early stages, it has some promising results. Hence, many companies are investing in the research of regenerative medicines. One of the leading names in that list is RepliCel Life Sciences, Inc. which provides tailor-made cell therapy products for aesthetics and orthopedics.

In an interview with Insights Care, Lee Buckler, the CEO of RepliCel, shares the journey of his company, its role in the development of regenerative

medicines, and the future aspects of the medical sector. Below are the highlights of the interview: Please brief our audience about RepliCel, its USPs, and the aspects that make it a leading name in the regenerative medicine space. RepliCel Life Sciences is a regenerative medicine company focused on developing cell therapies for aesthetic and orthopedic conditions aﬀecting what the company believes is approximately one in three people in industrialized nations, including aging/sun-damaged skin, male and female pattern baldness due to androgenetic alopecia, and chronic

We are focused on developing cell therapies for aesthetic and orthopedic conditions.

tendinopathies such as Achilles' tendinosis, Patellar Tendinosis ('Jumper's Knee'), Lateral Epicondylitis ('Tennis Elbow'), Golfer's Elbow, etc. The company's cell therapy product pipeline is comprised of RCT-01 for tendon repair, RCS-01 for skin rejuvenation, and RCH-01 for hair restoration. These conditions, often associated with aging, are caused by a deﬁcit of healthy cells required for normal tissue healing and function. These cell therapy product candidates are manufactured using RepliCel's innovative technology, starting with cell populations isolated from a patient's healthy hair follicles. RDH-01, having successfully met the endpoints in two completed clinical studies, is currently the subject of a third clinical study in Japan being funded by Shiseido Company. RepliCel owns the unfettered rights to the product outside of Asia. RCT-01 and RCS-01 are the subject of a codevelopment and commercialization agreement in Greater China to YOFOTO (China) Health Company. RepliCel maintains the rights to these products outside of Greater China. No other regenerative medicine company has a manufactured and

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10 Most Innovative Regenerative Medicine Companies in 2022

About the Leader

R. Lee Buckler CEO

regulated product as far along in clinical development for the treatment of hair loss as RepliCel's RCH-01. Similarly, no other regenerative medicine company has a manufactured and regulated product in clinical development with clinical data showing as much promise as RepliCel's RCS-01 to regenerate the extra-cellular matrix under aging or sun-damaged skin, which is currently the target of the >2-billion-dollar dermal ﬁller market.

RepliCel's CEO, Lee Buckler, has been in the regenerative medicine space since 2000, having served executive roles in contract manufacturing, nonproﬁt, consulting, technology services, and cell therapy product development organizations. He has continued RepliCel's early direction of securing regional co-development and commercialization partners and been instrumental in positioning RepliCel as one of the most active foreign cell therapy companies in Japan.

RepliCel is one of the few regenerative medicine companies developing a proprietary delivery system (DermaPreciseTM) optimized for local delivery of cells into the skin and underlying tissue, and this platform will be available for other companies to use in the delivery of their injectable products ranging from other cell

therapies to drugs, enzymes, toxins, antibodies, etc. RepliCel's proprietary injection system and related consumables are expected to improve the administration of its cell therapy products and any other injectable product being injected into the dermis or subcutaneous region of

RepliCel's RCT-01 is one of the leading cell-based regenerative medicines in clinical development for the treatment of tendinopathies which is a signiﬁcant and large unmet medical need. What other solutions and services does RepliCel oﬀer that gives it a leading edge over its competitors?

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think they 'should' do. If they're doing what they love, they'll be good at it, and their career will reward them. For those loving change and always being on the cutting edge of discovery and technology, biotechnology is one of the most rewarding industries. How do you envision scaling RepliCel's operations and oﬀerings in 2022 and beyond?

the skin and for which precision of depth, dose, and/or delivery is important for safety and/or eﬃcacy. YOFOTO has exclusively licensed the commercial rights for the DermaPreciseTM device and consumables for dermatology applications in Greater China and is expected to ﬁrst launch the product in Hong Kong upon it being approved for market launch in either the United States or Europe. RepliCel maintains all global rights to manufacturing and further development and maintains commercial rights outside of Greater China. MainPointe Pharmaceuticals holds the exclusive distribution rights for the DermaPreciseTM device and consumables for a limited time in the United States. With constant development in medical technologies, in your opinion, what could be the future of the regenerative medicine space? The life sciences sector is now in a position where we understand the

genetic or cellular causes of many human conditions. Once we understand the genetic or cellular deﬁcits or dysfunction underlying acute and chronic conditions, we can develop genetic or cellular therapeutic approaches which do not target palliative solutions but rather aim to be curative. Matching cellular or genetic deﬁcits with cellular or genetic solutions address the underlying condition in a way that few if any, predecessor therapeutic modalities accomplish. This is the promise of regenerative medicine, and it is clearly now wellentrenched as a future pillar of healthcare.

RepliCel's three cell therapy products have now been tested in over 100 patients in four countries on three continents. RepliCel now has key strategic partners in the United States, China, and Japan, each of which is now investing heavily in the further clinical testing and development of RepliCel's products for their markets. Data from each of the clinical programs will strengthen the product development initiatives for RepliCel and its other partners worldwide. Speciﬁcally, in Japan, where regulators have created two very unique commercialization pathways for regenerative medicine products, RepliCel is one of the leading foreign companies actively engaged in regulatory review, clinical development, and partnering to position its products for early commercialization. Finally, we expect to bring our dermal injector technology across the development and testing line culminating in a submission for marketing approval to the FDA.

As an established leader, what would be your advice to the budding professionals aspiring to venture into the biotech industry? My advice to all budding professionals, regardless of the industry, is to let their career follow their interests regardless of what education they took, or they

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