A 2nd Patient Death Reported in Novartis’ Gene Therapy Trial

biospace | April 22, 2019

Just as Novartis and AveXis’ gene therapy, Zolgensma (onasemnogene abeparvovec-xioi) for spinal muscular atrophy (SMA) is progressing toward approval, a second patient death was reported. Last week, AveXis, a Novartis  company, announced interim data from its Phase III STR1VE clinical trial of Zolgensma in SMA Type 1. SMA is a severe neuromuscular disease caused by a mutation in the SMN1 gene, which codes for SMN, a protein necessary for motor neuron function. The disease is noted by the loss of motor neurons, which leads to progressive muscle weakness and paralysis. It is rare, occurring in about one in 10,000 live births. Type 1 is lethal and typically results in death by the age of two years. Zolgensma is a gene therapy in development as a one-time infusion for SMA Type 1. It uses a virus vector to deliver a copy of the human SMN gene. In December, the Food and Drug Administration (FDA) accepted AveXis’ Biologics License Application (BLA) for Zolgensma, with a target action date in May 2019. It is also expected to be approved in Japan and the European Union later this year.

Spotlight

Outsourcing has been labelled as one of this century’s “greatest organizational and industry structure shifts”.The general model in the pharmaceutical and biotechnology industries sees market authorization holders (MAH) rely on external partners to execute a range of activities including the likes of research, development and manufacturing.Rising pressure from the public regarding medicine price points compounds the appeal of outsourcing as a route to cool costs and free up internal resource burdens.

Spotlight

Outsourcing has been labelled as one of this century’s “greatest organizational and industry structure shifts”.The general model in the pharmaceutical and biotechnology industries sees market authorization holders (MAH) rely on external partners to execute a range of activities including the likes of research, development and manufacturing.Rising pressure from the public regarding medicine price points compounds the appeal of outsourcing as a route to cool costs and free up internal resource burdens.

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CELL AND GENE THERAPY

Adicet Bio Reports Inducement Grants under Nasdaq Listing Rule 5635(c)(4)

Adicet Bio, Inc. | September 06, 2022

Adicet Bio, Inc. a clinical-stage biotechnology company discovering and developing allogeneic gamma delta CAR T cell therapies for cancer, today announced it granted inducement awards on August 31, 2022 under Adicet’s 2022 Inducement Plan as a material inducement to employment to five individuals hired by Adicet in August 2022. The employees received, in the aggregate, non-qualified stock options to purchase 114,200 shares of Adicet’s common stock with an exercise price of $14.16 per share, the closing price of Adicet’s common stock as reported by Nasdaq on August 31, 2022. One-fourth of the shares underlying each employee’s option will vest on the one-year anniversary of each recipient’s start date and thereafter the remaining three-fourths of the shares underlying each employee’s option will vest in thirty-six substantially equal monthly installments, such that the shares underlying the option granted to each employee will be fully vested on the fourth anniversary of the recipient’s start date, in each case, subject to each such employee’s continued employment with Adicet on such vesting dates. All of the above-described awards were granted outside of Adicet’s stockholder-approved equity incentive plans pursuant to Adicet’s 2022 Inducement Plan, which was adopted by the board of directors in January 2022. The awards were authorized by the compensation committee of the board of directors, which is comprised solely of independent directors, as a material inducement to the employees entering into employment with Adicet in accordance with Nasdaq Listing Rule 5635(c)(4). About Adicet Bio, Inc. Adicet Bio, Inc. is a clinical-stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for cancer. Adicet is advancing a pipeline of “off-the-shelf” gamma delta T cells, engineered with chimeric antigen receptors and T cell receptor-like antibodies to enhance selective tumor targeting, facilitate innate and adaptive anti-tumor immune response, and improve persistence for durable activity in patients.

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CELL AND GENE THERAPY

Sesen Bio and Carisma Therapeutics Announce Merger Agreement

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. 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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. 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INDUSTRIAL IMPACT

New Data Reveal Molecular Drivers of Thyroid Eye Disease (TED) May Remain Activated In Patients with Low Clinical Activity Score (CAS)

Horizon | October 03, 2022

Horizon Therapeutics plc announced the presentation of new data defining molecular patterns in TED and further implicating the role of insulin-like growth factor-1 in patients with low CAS. These data were presented during the American Academy of Ophthalmology Annual Meeting Sept. 30 – Oct. 3 in Chicago. TED is a progressive and potentially vision-threatening rare autoimmune disease, which has been historically characterized as biphasic: acute, which is traditionally believed to be patients with high CAS and earlier in their TED journey; and chronic, traditionally believed to be patients with low CAS and later in the course of their disease.1 This analysis reveals that in patients with both high and low CAS, there is clear activation of IGF-1 and related pathways, as well as the extracellular matrix organization, a structural network that supports cellular processes.2 “By demonstrating that disease activity remains in patients with low CAS, this analysis may help explain why many patients who have lived with Thyroid Eye Disease for several years are still struggling with challenging symptoms that can be debilitating. It is important for physicians to be aware of the continued activation of IGF-1 throughout the course of the disease and its potential impact on treatment decisions.” Shoaib Ugradar, M.D., The Jules Stein Eye Institute at University of California, Los Angeles The study analyzed genome ribonucleic acid sequencing and pathway analysis in orbital tissue from patients with a CAS of ≥ 3 and patients with a CAS ≤ 2, as well as five control subjects. Though high CAS patients are often distinguished by activation of immune system pathways, which remain largely unaffected in low CAS patients, IGF-1 and its related pathways were found to be upregulated in both stages of disease. Additional analysis suggests that IGF-1 activity plays a central role in linking immune and ECM pathways in people with TED.2 The upregulation of IGF-1 found in low CAS patients with extended disease duration is further supported by a growing body of evidence that outlines the impact of TED on people who have lived with it for several years.3 One assessment published in the journal Ophthalmology and Therapy in 2021 found that disease burden continues well into the chronic phase, affecting daily lives with appearance and persistent visual changes, increasing risk for anxiety and depression.4 “This study, which represents one of the first molecular analyses of the continuum of Thyroid Eye Disease, confirms this challenging disease may not simply subside after a few years of obvious symptoms,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, chief medical officer, Horizon. “We are committed to pioneering research like this to better understand drivers of the evolution of this disease in order to better support patients living with Thyroid Eye Disease across the course of their lifetimes.” About Thyroid Eye Disease. TED is a serious, progressive and potentially vision-threatening rare autoimmune disease.1 TED often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an IGF-1R-mediated signaling complex on cells within the retro-orbital space.5,6 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness. Early signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and diplopia.7,8 About Horizon Horizon is a global biotechnology company focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives.

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