• World Biz Magazine

PAUL K. WOTTON, CEO OBSIDIAN THERAPEUTICS - INTERVIEW WITH WBM TOP 100 INNOVATION CEO



PAUL K. WOTTON, CEO OBSIDIAN THERAPEUTICS HAS BEEN SELECTED BY THE JUDGES OF WORLD BIZ MAGAZINE'S ANNUAL AWARDS TO BE A RECIPIENT OF THE TOP 100 CEOS IN INNOVATION AWARD 2021. THIS SELECTION FOLLOWS A STRINGENT PROCESS THAT EVALUATED OVER 40,000 NOMINEES TO SELECT THE EXCLUSIVE LIST OF 100 WINNERS.


Dr. Paul K. Wotton is Obsidian’s Chief Executive Officer, bringing significant experience spanning scientific research, product development and corporate growth gained over a thirty-year career.


Dr. Wotton most recently served as the Founding President and CEO of Sigilon Therapeutics, Inc. Prior to Sigilon, Dr. Wotton served as President and Chief Executive Officer of Ocata Therapeutics until its acquisition by Astellas Pharma where he was also Co-Chairman of the Office of Integration. In previous roles, he served as President and Chief Executive Officer of Antares Pharma (NASDAQ:ATRS) as well as Chief Executive Officer of Topigen Pharmaceuticals.


Dr. Wotton is a named inventor on numerous patents and was the Ernst & Young Entrepreneur of the Year Regional (NJ) Winner Life Sciences in 2014. He serves on the Boards of Directors of Vericel Corporation (NASDAQ: VCEL), Veloxis Pharmaceuticals A/S (Copenhagen: VELO) and Cynata Therapeutics (ASX: CYP) as its Chairman.


What are some of the recent highlights at Obsidian?

In April 2021, Obsidian and Vertex Pharmaceuticals entered into a strategic research collaboration and licensing agreement focused on the discovery of novel therapies that regulate gene editing for the treatment of serious diseases. The collaboration leverages Obsidian’s cytoDRiVE® platform technology to discover gene-editing medicines whose therapeutic activity can be precisely controlled using small molecules and Vertex’s established scientific and clinical capabilities in small molecule, cell, and genetic therapies to bring these approaches more rapidly to patients. The collaboration includes an upfront payment and also equity investment by Vertex, and potential future milestone and royalty payments.


Obsidian and MD Anderson Cancer Center entered a multi-year collaboration in November 2020 designed to expedite the research and development of novel engineered tumor infiltrating lymphocytes (TILs) for the treatment of solid tumors. The collaboration is focused on developing TILs armored with regulated membrane-bound IL15 (referred to as cytoTIL™) with the potential to enhance anti-tumor efficacy and reduce tumor burden in patients suffering from different types of solid tumors. By leveraging regulated membrane-bound IL15 to drive antigen-independent expansion of T cells and transactivation of NK cells, cytoTIL therapy is anticipated to improve patient response to TIL treatment and expand patient eligibility to those who currently cannot benefit from this transformative therapy.


Share with us some of the key innovations at Obsidian that have been gaining attention in the industry.

Innovation is the foundation of our company from which we draw revenue. Our proprietary cytoDRiVE® platform, which leverages drug responsive domains (DRDs) to control protein function using an FDA-approved small molecule, can be married to third-party cell and gene therapies, enabling our biopharmaceutical colleagues to innovate upon their own technologies that may otherwise not make it to market.


Our latest venture is to innovate a solution for the limitations of tumor-infiltrating lymphocytes (TIL). Due to toxicity, the IL-2 regimen required for in vivo maintenance of TILs poses significant limitations on application of the therapy. Obsidian’s cytoTIL™ product is comprised of TILs engineered with membrane bound IL-15 (mbIL15) that is regulatable using a drug responsive domain (DRD) designed via our cytoDRiVE™ platform, allowing for TILs to be effective without the toxic infusions of IL-2.


Why is Obsidian's cytoDRiVE™ platform a particularly exciting opportunity for your partners and what does it mean for the industry in general?

Our cytoDRiVE™ platform makes life-saving therapies that need a concentration control mechanism to work possible. Said best by our partners, Vertex and MD Anderson, respectively, “The ability to tune gene-editing activity to a specific level is an important innovation that has the potential to address several serious diseases.”

“By controlling the expression of armed payloads like CD40L, Obsidian’s cell therapy candidates may have the potential to overcome tumor microenvironment resistance and unlock the power of cell therapy in solid tumors and other malignancies.”


Please give a summation of the current state of the industry and what improvements you believe are necessary.

The industry has only just begun to develop cell and gene therapies, the vast majority of technologies still being preclinically evaluated. Given their potential to treat the untreatable, we desire to see an increase in the rate of transition from preclinical to clinical studies. We want to reduce the number of dead ends. Obsidian’s cytoDRiVE™ and cytoTIL™ technologies can improve the function of therapeutics held back in preclinical studies, moving them to the clinic. The failure rate in our industry is notoriously high. We hope to reach potential collaborators with our technology before they end trials and pursue other assets in their pipeline.


What makes a good leader?

A good leader is a visionary, someone with the expertise and foresight of where to go and what strategic actions to take next. A good leader is an effective delegator, someone who really understands and invests in the strengths and plans for the weaknesses of their team. A good leader is a clear communicator, someone who delegates tasks with clear directions and expectations, setting their team members up for success. A good leader is empathetic, someone who uplifts and empowers their team by making them feel valued, recognizing them as humans first before thinking about them as employees.


"We believe TILs represent the most promising cell therapy approach to address the significant factors which have to date limited the effectiveness of therapies for patients with solid tumor malignancies."

Obsidian is pioneering engineered cell and gene therapies - talk to us about the potential for patients?

Cell therapies have immense potential to change the way we treat cancer. Obsidian’s lead program is an engineered tumor infiltrating lymphocyte (“TIL”) therapy with membrane-bound IL15 (mbIL15) – called cytoTIL15 – for patients with solid tumors. cytoTIL15 eliminates the need for concomitant IL2 therapy (a toxic and costly requirement for conventional TILs) and drives improved efficacy (magnitude and duration of response).


Elimination of IL2 from the TIL treatment regimen is a game changer for cancer patients, and comprehensive KOL research suggests that this advancement alone will disrupt the TIL market by (1) displacing conventional TIL therapy and (2) expanding patient eligibility by 50% to capture patients who cannot tolerate or access IL2 therapy, such as patients who are elderly, frail, or have complications from prior treatment regimens.


Obsidian’s cytoTIL15 is expected to drive improved efficacy by leveraging the benefits of mbIL15. Our preclinical data across numerous in vitro and in vivo assays demonstrate enhanced potency and persistence of cytoTIL15 (without IL2) vs. conventional TIL + IL2. Enhanced T-cell persistence in TIL therapy has been correlated with more durable responses and improved patient outcomes in the clinic.


Share with us some insight into the market potential.

We believe TILs represent the most promising cell therapy approach to address the significant factors which have to date limited the effectiveness of therapies for patients with solid tumor malignancies, including tumor antigen heterogeneity and the impact of an immunosuppressive tumor microenvironment. TILs are polyclonal by nature and able to recognize multiple tumor antigens. Since they are personalized to the T cells of a specific patient, TILs have already recognized the tumor and exhibit strong homing properties. And importantly, we know they work: TILs have shown promising, durable responses in multiple solid tumor indications, most notably in heavily pre-treated patients with metastatic melanoma and cervical cancer. cytoTIL15 holds significant commercial potential in solid tumors. By eliminating IL2 and improving efficacy vs. conventional TIL therapies, cytoTIL15 has the potential to displace conventional TIL therapies (e.g., those under development by Iovance, InstilBio) and expand patient eligibility to at least 50% more patients suffering from solid tumors.


Why the name Obsidian?

Obsidian is a volcanic glass that is used to create exceptionally sharp precision blades. Our namesake illustrates our approach in engineering precise cell and gene therapies specific to each patient. Like the diversity of Obsidian sources, our team reflects diverse backgrounds, identities, and experiences.


What drives you and how is this reflected in your team?

A few years ago, I stepped down from my role as the CEO of Sigilon Therapeutics to care for a family member as they received chemotherapy. This experience inspired me to focus my future efforts toward oncology which eventually brought me to Obsidian. At Obsidian, we are pioneering safe and effective engineered cell and gene therapies for cancer and other serious diseases. Our team is composed of curious, energetic, yet disciplined problem-solvers motivated by making cell and gene therapies safer as well as more accessible. During the pandemic, our team developed SWFT (Safe Workplace Function Tool), an application to manage personnel and lab equipment, so that we could continue to progress research and maintain productivity. We’ve also made this software freely available to other biotech firms. By effectively adapting to challenges, Obsidian has continued to progress development of engineered cell and gene therapies in an effort to provide transformative outcomes for patients.


Find out about Obsidian Therapeutics: www.obsidiantx.com