CELL AND GENE THERAPY
Sesen Bio and Carisma Therapeutics | September 22, 2022
Sesen Bio, Inc. and Carisma Therapeutics Inc. a privately held, clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, announced that they have entered into a definitive merger agreement to combine the companies in an all-stock transaction. The combined company will focus on the advancement of Carisma’s proprietary cell therapy platform that utilizes engineered macrophages and monocytes to potentially transform the treatment of cancer and other serious disorders. Carisma is pioneering the development of chimeric antigen receptor macrophage therapies and is believed to be the only company developing CAR-M therapies with demonstrated proof of mechanism and safety data in clinical trials. The combined company is expected to operate under the name Carisma Therapeutics Inc. and trade on Nasdaq under the ticker symbol “CARM”.
Carisma has also secured commitments from a syndicate of investors for a $30 million financing, including HealthCap, AbbVie, Wellington Partners, SymBiosis, Penn Medicine, TPG Biotech, MRL Ventures Fund, the therapeutics-focused corporate venture arm of Merck & Co., Agent Capital, Solasta, Livzon, Pictet Alternative Advisors and 4Bio, which is expected to close concurrently with the completion of the merger. With the cash expected from both companies at closing and the proceeds of the concurrent financing, the combined company is expected to have approximately $180 million in cash, cash equivalents and marketable securities. These cash resources are expected to be used to advance Carisma’s pipeline through multiple ongoing and planned key data readouts across several clinical trials and to fund operating expenses and capital expenditure requirements through 2024. The merger and related financing are expected to close in the next three to four months.
“The proposed merger represents an exciting opportunity for shareholders of each company, and we believe it gets us one step closer to our goal of revolutionizing the field of immunotherapy. This transaction will provide us with financial strength to not only continue to develop our lead candidate CT-0508, but also allow us to accelerate the growth of our platform and pipeline within and outside of oncology and develop additional strong strategic partnerships beyond those we already have with Moderna and Novartis. Carisma is focused on delivering cutting-edge technology for patients in a way that has never been done before, and we look forward to advancing this important mission.”
Steven Kelly, President and Chief Executive Officer of Carisma
“This transaction represents the result of a thoughtful and careful review of strategic alternatives over the past four months, during which Carisma’s clinical programs, management team, and corporate strategy stood out amongst the 42 bids reviewed,” said Dr. Thomas Cannell, President and Chief Executive Officer of Sesen Bio. “Carisma is an exciting clinical-stage company with groundbreaking science and an impressive management team, which we believe makes them the optimal partner to provide value for our shareholders. Our mission at Sesen Bio has always been to save and improve the lives of patients with cancer, and we believe Carisma has the science and the unwavering patient focus required to make that mission a reality.”
About the Proposed Merger
Pre-merger Sesen Bio stockholders are expected to own approximately 41.7% and pre-merger Carisma stockholders are expected to own approximately 58.3% of the combined company, in each case before giving effect to the concurrent financing described above and the conversion of the outstanding Moderna convertible note. Under the terms of the merger agreement, stockholders of Carisma will receive newly issued shares of Sesen Bio common stock pursuant to an exchange ratio formula set forth in the merger agreement. The percentage of the combined company that Sesen Bio stockholders will own upon the closing of the merger is further subject to adjustment based on the amount of Sesen Bio’s net cash at the time of closing.
Immediately prior to the closing of the proposed merger, Sesen Bio stockholders of record will be issued a contingent value right (CVR) for each outstanding share of Sesen Bio common stock held by such Sesen Bio stockholder as of such date, representing the right to receive certain cash payments from proceeds received by Sesen Bio related to the Roche Asset Purchase Agreement, if any, subject to customary deductions, including for expenses and taxes.
SVB Securities is acting as exclusive financial advisor to Sesen Bio for the transaction and Hogan Lovells US LLP is serving as its legal counsel. Evercore Group LLC is serving as lead financial advisor to Carisma for the transaction and BofA Securities, Inc. is also serving as financial advisor to Carisma for the transaction. Wilmer Cutler Pickering Hale and Dorr LLP is serving as legal counsel to Carisma. BofA Securities, Inc. and Evercore Group L.L.C. are serving as co-placement agents for Carisma’s concurrent financing and Shearman & Sterling LLP is serving as the placement agents’ legal counsel.
About Sesen Bio
Sesen Bio, Inc. is a late-stage clinical company focused on targeted fusion protein therapeutics for the treatment of patients with cancer. Sesen Bio’s most advanced product candidate, Vicineum™, also known as VB4-845, is a locally-administered targeted fusion protein composed of an anti-epithelial cell adhesion molecule antibody fragment tethered to a truncated form of Pseudomonas exotoxin A for the treatment of non-muscle invasive bladder cancer. On July 15, 2022, Sesen Bio made the strategic decision to voluntarily pause further development of Vicineum in the US. The decision was based on a thorough reassessment of Vicineum, which included the incremental development timeline and associated costs for an additional Phase 3 clinical trial, following Sesen Bio’s discussions with the United States Food and Drug Administration. Sesen Bio has turned its primary focus to assessing potential strategic alternatives with the goal of maximizing shareholder value. Additionally, Sesen Bio intends to seek a partner for the further development of Vicineum.
About Carisma Therapeutics
Carisma Therapeutics Inc. is a biopharmaceutical company dedicated to developing a differentiated and proprietary cell therapy platform focused on engineered macrophages, cells that play a crucial role in both the innate and adaptive immune response. The first applications of the platform, developed in collaboration with the University of Pennsylvania*, are autologous chimeric antigen receptor (CAR)-macrophages for the treatment of solid tumors. Carisma Therapeutics is headquartered in Philadelphia, PA.
Athersys, Inc. | September 26, 2022
Athersys, Inc. a regenerative medicine company developing MultiStem® for critical care indications, announced that it has entered into amended agreements to extend the exercise period of the warrants that were issued as part of a registered direct offering that closed on August 17, 2022, among other changes, and to issue additional warrants to the same warrant holder, a healthcare-focused U.S. institutional investor.
The Purchase Agreement contains certain restrictions that, subject to certain exceptions, prohibit the Company from issuing its common stock in certain variable rate transactions for a period of 180 days following the Closing Date. The Purchase Agreement also gives the Purchasers the right to participate in certain future offerings of the Company in an amount of up to 30 percent in the aggregate of any offered securities during the 12 months following the Closing Date.
On September 22, 2022, the Company entered into an amendment to the Purchase Agreement with the Purchasers to, among other things, (i) extend the exercise period of the Initial Warrants from five years to seven years after the six-month anniversary of the Closing Date (the “Warrant Amendment”), (ii) reduce the Standstill Period from 180 days to 150 days following the Closing Date, (iii) reduce the term and amount of the Participation Right from twelve months to six months following the Closing Date and from 30 percent to 20 percent in the aggregate of any offered securities, respectively, and (iv) require the Purchasers, subject to certain conditions, to participate in the event the Company proposes to offer and sell shares of offered securities during the six months following the Closing Date to investors primarily for capital raising purposes.
In return, Athersys issued to the same warrant holder additional warrants that are exercisable for an aggregate of 2,000,000 shares of common stock and have an exercise price of $6.3850 for a seven-year period after the six-month anniversary of the date of issuance.
A more detailed discussion of the amendments is contained in a Current Report that Athersys filed on September 22, 2022 with the U.S. Securities and Exchange Commission on Form 8-K.
“We are pleased to have entered into this amendment with our new major investor which provides more financial flexibility going forward as well as a commitment for the investor that recently invested $12 million in Athersys to participate in future financings if requested. As Athersys continues to pursue licensing and other business development opportunities for our proprietary technology this amendment can help facilitate future transactions with financial and strategic investors. We are fortunate to have established a strong relationship with a prominent healthcare focused institutional investor that embraces the value of our MultiStem cell therapy and is responsive to our priorities,”
Dan Camardo, Chief Executive Officer of Athersys
“I am also pleased with progress we’ve made in our business transformation and I look forward to updating shareholders during a conference call to be held the week of October 3rd,” he added.
Athersys intends to issue a separate news release that will provide further information on the date and time of the call, as well as instructions regarding how to participate.
MultiStem® cell therapy is a patented regenerative medicine product in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors in response to signals of inflammation and tissue damage. MultiStem therapy’s potential for multidimensional therapeutic impact distinguishes it from traditional biopharmaceutical therapies focused on a single mechanism of benefit. The therapy represents a unique “off-the-shelf” stem cell product that can be manufactured in a scalable manner, may be stored for years in frozen form, and is administered without tissue matching or the need for immune suppression. Based upon its efficacy profile, its novel mechanisms of action, and a favorable and consistent tolerability demonstrated in clinical studies, we believe that MultiStem therapy could provide a meaningful benefit to patients, including those suffering from serious diseases and conditions with unmet medical need.
Athersys is a biotechnology company engaged in the discovery and development of therapeutic product candidates designed to extend and enhance the quality of human life. The Company is developing its MultiStem® cell therapy product, a patented, adult-derived “off-the-shelf” stem cell product, initially for disease indications in the neurological, inflammatory and immune, and other critical care indications and has several ongoing clinical trials evaluating this potential regenerative medicine product. Athersys has forged strategic partnerships and a broad network of collaborations to further advance MultiStem cell therapy toward commercialization.
CELL AND GENE THERAPY
Genscript Biotech Corporation | September 23, 2022
GenScript USA Inc., the world's leading life-science research tools and services provider, is collaborating with researchers at the Gladstone-UCSF Institute of Genomic Immunology to advance the development of new, non-viral cell therapies that modify genomic sequences in the pursuit of more effective cell therapy products while limiting the cellular toxicity that is typically associated with previously available methods.
A new study, published in Nature Biotechnology, details methods for achieving highly efficient non-viral knock-in using GenScript's GenExact™ single-strand DNA modified with Cas9-target sequences. This method achieved up to ˜40% knock-in efficiency in primary immune cell types.
One powerful application of CRISPR/Cas genome editing technology involves the precise insertion of DNA sequences via the HDR pathway. Traditionally, researchers have relied on viral vectors to deliver DNA insertion templates used for gene therapy into cells. However, difficulties manufacturing large amounts of clinical-grade viral vectors have delayed getting cell therapies to patients. Additionally, viral vectors can insert genes at any location within the genome, leading to safety concerns.
Previous research by the group at Gladstone and UCSF has shown that synthetic DNA templates can be delivered without the use of viral vectors, but high levels of double-stranded DNA can be toxic to cells, resulting in low efficiency. Efficiency can be improved using a modified version of the DNA templates that can bind to the Cas9 enzyme. However, additional work was required to improve the yield of successfully engineered cells and to make the process compatible with the manufacturing of future cell therapies. Those goals motivated the team's current study.
In this study, the team tested modified GenExact ssDNA designed with Cas9-targeted sequences to determine if the gene-editing efficiency could be improved with lower toxicity. First, synthetic sgRNA was complexed with Cas9 protein to form a RNP complex. Then the RNP and ssDNA template were delivered into the cell via electroporation, enabling efficient gene editing.
The team discovered that this combination of GenExact ssDNA with Cas9-targeted sequence offers up to 40% knock-in editing efficiency with minimal cellular toxicity. This approach can accelerate the development and manufacture of novel, high-yield non-viral gene therapies — and at lower cost.
"We are very proud to have collaborated on this groundbreaking scale-up work by the talented team at Gladstone and UCSF. GenScript is excited for the opportunities that this high-yield cell-line engineering process will provide to our customers," said Ray Chen, Ph.D, president of GenScript Life Science Group.
"We were very happy to partner with Genscript on critical experiments demonstrating high efficiency and yield of CAR knock-in cells at clinical scale. The long ssDNA produced by Genscript exceeded our expectations and helped us clearly demonstrate the potential for future therapeutic applications using these methods.",
Brian Shy, MD, PhD, a former clinical fellow in the lab of Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology
About GenScript Biotech Corporation
GenScript Biotech Corporation is a global biotechnology group. Based on its leading gene synthesis technology, GenScript has developed four major platforms including the global cell therapy platform, the biologics contract development and manufacturing organization platform, the contract research organization platform, and the industrial synthesis product platform.
GenScript was founded in New Jersey, USA in 2002 and listed on the Hong Kong Stock Exchange in 2015. GenScript's business operation spans over 100 countries and regions worldwide, with legal entities located in the USA, mainland China, Hong Kong, Japan, Singapore, the Netherlands, and Ireland. GenScript has provided premium, convenient, and reliable products and services for over 100,000 customers.