On September 21, 2022 Sesen Bio, Inc. (Nasdaq: SESN) and Carisma Therapeutics Inc. (Carisma), a privately held, clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that they have entered into a definitive merger agreement to combine the companies in an all-stock transaction (Press release, Sesen Bio, SEP 21, 2022, View Source [SID1234621297]). 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 (CAR-M) 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".

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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.

Carisma’s cell and gene therapies are based on a proprietary platform technology that reprograms a patient’s macrophages and targets them against cancer cells, with the potential for broad anti-tumor immunity. This novel technology is designed to engage with the body’s immune system to treat solid tumors, which remains a persistent clinical challenge that is yet to be comprehensively achieved through CAR-T and other immunotherapy approaches.

Carisma’s CAR-M platform provides the ability to fine-tune the specific targets of the immune cells, potentially enabling multiple therapeutic applications in and beyond oncology. The first clinical application of this technology is CT-0508, a CAR-M cell therapy currently being evaluated by Carisma in a Phase 1 multi-center clinical trial with a lead target indication of advanced HER2+ solid tumors. Carisma believes this Phase 1 clinical trial marks the first time that engineered macrophages are being studied in humans. Carisma is leveraging its proprietary CAR-M platform to expand its oncology pipeline both independently and through a strategic partnership with Moderna. Additionally, Carisma is exploring the potential to develop its proprietary macrophage engineering platform for non-oncology applications such as liver fibrosis, as well as autoimmune and neurodegenerative disease indications.

"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," said Steven Kelly, President and Chief Executive Officer of Carisma. "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."

"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."

Carisma has several anticipated upcoming catalysts and developmental milestones across its clinical programs over the next 18 months, including:

Additional Phase 1 data readout of safety, manufacturing feasibility, and mechanism of action of CT-0508 with single-day dosing
Completion of the technology transfer to Novartis for the planned clinical manufacturing of CT-0508
Phase 1 data readout for the CT-0508 intraperitoneal trial for patients with HER2+ peritoneal cancer
Phase 1 data readout of CT-0508 in combination with pembrolizumab for patients with HER2+ solid tumors
Investigational New Drug (IND) Application for a new HER2 CAR engineered monocyte cell product
In addition to its exclusively licensed proprietary technologies that were developed by leading scientists at the University of Pennsylvania (Penn), including Saar Gill, MD, PhD, an associate professor of Medicine at Penn’s Perelman School of Medicine and a Carisma co-founder and fellow co-founder and Carisma’s Chief Scientific Officer, Dr. Michael Klichinsky, PharmD, PhD, Carisma has well-established strategic partners to support the advancement of its pipeline. Carisma recently entered into a strategic partnership with Moderna for the discovery, development and commercialization of in vivo CAR-M therapies for up to 12 targets for the treatment of cancer. As part of the collaboration, Carisma received a $45 million up-front cash payment and an investment by Moderna in the form of a $35 million convertible note, which will convert into shares of common stock of the combined company in connection with the merger. Under the collaboration, Carisma will receive full research funding and is eligible to receive development, regulatory, and commercial milestone payments, plus royalties on net sales of any products that are commercialized. Carisma has also partnered with Novartis, which has extensive experience in cell therapy manufacturing, to operate as Carisma’s contract manufacturing organization for clinical supply of its lead clinical program, CT-0508.

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.

Following the consummation of the merger, the combined company will be headquartered in Philadelphia, Pennsylvania, and will be led by Steven Kelly, President and Chief Executive Officer of Carisma. Mr. Kelly was recently named Ernst & Young Entrepreneur of the Year 2022 Greater Philadelphia, an award that recognizes the most ambitious leaders who are building and sustaining successful, dynamic businesses around the world. The board of directors of the combined company is expected to be composed of seven members, consisting of one member designated by Sesen Bio and six members designated by Carisma.

The merger agreement has been unanimously approved by the boards of directors of both companies. The merger and related financing are expected to close in the next three to four months, subject to approval by Sesen Bio’s shareholders and other customary closing conditions.

Additional information about the transaction will be provided in a Current Report on Form 8-K that will be filed by Sesen Bio with the Securities and Exchange Commission (SEC) and will be available at www.sec.gov.

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.

On September 21, 2022 Fennec Pharmaceuticals Inc. (NASDAQ: FENC; TSX: FRX), a specialty pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has approved PEDMARK (sodium thiosulfate injection) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients one month of age and older with localized, non-metastatic solid tumors (Press release, Fennec Pharmaceuticals, SEP 21, 2022, View Source [SID1234621296]). This approval makes PEDMARK the first and only treatment approved by the FDA in this area of significant unmet medical need.

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"The FDA approval of PEDMARK represents an important breakthrough for pediatric patients with localized, non-metastatic solid tumors at risk for cisplatin-induced hearing loss. Cisplatin is a critical, standard of care agent, used in the treatment of pediatric cancers; however, even though effective, it could be harmful to children, frequently causing permanent and irreversible bilateral hearing loss. With PEDMARK, physicians now have an approved treatment option to reduce the risk of cisplatin-induced hearing loss in pediatric patients," said Rosty Raykov, chief executive officer of Fennec Pharmaceuticals. "We would like to thank the patients, their families, physicians, investigators, employees, consultants and the entire research team at Oregon Health and Science University, who have contributed to the development of PEDMARK."

The FDA approval of PEDMARK was based upon safety and efficacy data from two pivotal open-label, randomized Phase 3 trials (SIOPEL 6 and COG ACCL0431), which compared PEDMARK plus cisplatin-based regimen to cisplatin-based regimens alone for the reduction of cisplatin-induced hearing loss in pediatric patients. In both studies, the incidence of hearing loss was consistently and significantly lower in the PEDMARK plus cisplatin arm compared with the cisplatin alone arm [21.4% vs. 73.3% (p = 0.005) and 32.7% vs. 63% (p = 0.002) with hearing loss in COG ACCLO431 and SIOPEL6, respectively]. The most common adverse reactions (≥ 25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL6 are vomiting, infection, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 is hypokalemia.

"Historically, there have been no approved treatments for preventing cisplatin-induced hearing loss. As a physician focused in pediatric cancer for many years, and a primary investigator in the pivotal PEDMARK Phase 3 Clinical Oncology Group (COG) trial, the FDA approval of PEDMARK addresses an enormous unmet need and for many children and young adults, has the potential to greatly improve everyday activities for these patients," said David R. Freyer, DO, MS, Primary Investigator, COG ACCL0431, and Director of the Survivorship & Supportive Care Program, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles.

Advances in chemotherapy-based treatment approaches for pediatric patients with localized, solid tumors have improved, resulting in an 85 percent or higher five-year survival rate for these patients2. However, use of platinum-based chemotherapy, still the treatment of choice in many cases, can be toxic to the ears and cisplatin treatment frequently causes permanent and irreversible bilateral (affecting both ears) hearing loss. Permanent hearing loss can be seen in approximately 60 percent of children treated with cisplatin and can be as high as 90 percent.1,2 Until now, interventions with management strategies such as cochlear implants and hearing aids only occurred after hearing loss had been detected and these interventions do not return normal hearing.3

"Hearing loss can have a profound impact on a person’s life, especially in children who are critically dependent upon normal hearing for cognitive, psychosocial, and speech development," said Penelope "Peppy" R. Brock, M.D., Ph.D., of Great Ormond Street Hospital in London and International Chair of the SIOPEL 6 trial. "Incorporating PEDMARK into current treatment strategies with the goal to preserve hearing in children and young adults without reducing the effectiveness of their cisplatin treatment – is a welcome step towards helping to improve long-term outcomes for these patients."

For more information about product availability and patient support, please contact the Fennec HEARS program at 1-833-7PEDMARK (1-833-773-3627).

The FDA granted this application Priority Review designation. PEDMARK also received Orphan Drug designation by the FDA in 2004.

The Marketing Authorization Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA).

About Cisplatin-Induced Ototoxicity
Cisplatin and other platinum compounds are essential chemotherapeutic agents for the treatment of many pediatric malignancies. Unfortunately, platinum-based therapies can cause ototoxicity, or hearing loss, which is permanent, irreversible, and particularly harmful to the survivors of pediatric cancer.4

The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids or cochlear implants, which can be helpful for some, but do not reverse the hearing loss and can be costly over time.5 Infants and young children that are affected by ototoxicity at critical stages of development lack speech and language development and literacy, and older children and adolescents often lack social-emotional development and educational achievement.6

About PEDMARK (sodium thiosulfate injection)
PEDMARK is the first and only U.S. Food and Drug Administration (FDA) approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in pediatric patients with localized, non-metastatic, solid tumors. It is a unique formulation of sodium thiosulfate in single-dose, ready-to-use vials for intravenous use in pediatric patients.7 PEDMARK is also the only therapeutic agent with proven efficacy and safety data with an established dosing paradigm, across two open-label, randomized Phase 3 clinical studies, the Clinical Oncology Group (COG) Protocol ACCL0431 and SIOPEL 6.

In the U.S. and Europe, it is estimated that, annually, more than 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult, and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit. Infants and young children that suffer ototoxicity at critical stages of development lack speech language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.

Indications and Usage
PEDMARK (sodium thiosulfate injection) is indicated to reduce the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors.

Limitations of Use
The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible ototoxicity may have already occurred.

Important Safety Information
PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or any of its components.

Hypersensitivity reactions occurred in 8% to 13% of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue PEDMARK and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocorticoids (if appropriate) before each subsequent administration of PEDMARK. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulfite sensitivity is seen more frequently in people with asthma.

PEDMARK is not indicated for use in pediatric patients less than 1 month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic cancers.

Hypernatremia occurred in 12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical trials, with Grade 3 or 4 occurring in 9% to 27% of patients. Monitor serum sodium and potassium at baseline and as clinically indicated. Withhold PEDMARK in patients with baseline serum sodium greater than 145 mmol/L.

Monitor for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73m2.

Administer antiemetics prior to each PEDMARK administration. Provide additional antiemetics and supportive care as appropriate.

The most common adverse reactions (≥25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL6 were vomiting, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction (≥25% with difference between arms of >5% compared to cisplatin alone) in COG ACCL0431 was hypokalemia.

On September 21, 2022 Evaxion Biotech A/S (NASDAQ: EVAX) ("Evaxion" or the "Company"), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies, reached an important milestone reported that it had enrolled its first patient in the global phase 2b clinical trial of EVX-01, the Company’s personalized cancer therapy for the treatment of melanoma (Press release, Evaxion Biotech, SEP 21, 2022, View Source [SID1234621295]).

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In the company’s first phase 2b clinical trial, Evaxion is evaluating the efficacy and safety of EVX-01 in adults with metastatic melanoma. The trial is being conducted globally at clinical sites across the US, Europe, and Australia in collaboration with Merck & Co., Inc., which is supplying the trial with its PD-1 inhibitor, KEYTRUDA.

Patients enrolled in the phase 2b clinical trial will receive standard of care treatment along with KEYTRUDA in combination with EVX-01. Evaxion is responsible for the conduct of the trial and Merck will supply the required KEYTRUDA. Evaxion and Merck will continue to collaborate as the data mature.

Erik Heegaard, Evaxion’s Chief Medical Officer, said:

"We are extremely proud to take EVX-01 into the next clinical development phase, enrolling our first patient in the clinic. We believe that this will help to support our efforts in developing new and more efficacious treatments for patients suffering from malignant melanoma. With this phase 2b trial, we are addressing a major unmet medical need in an indication that has become a multi-billion-dollar market. Together with our collaborators at Merck, we hope to further validate the promising data generated in our phase 1/2a study, which we believe may potentially pave the way for much needed improvement in the treatment landscape for melanoma and possibly other cancers."

Background:

●EVX-01 is a novel personalized cancer immunotherapy based on Evaxion’s proprietary PIONEER AI technology, for the treatment of patients with melanoma.
●Data from the Phase 1/2a clinical trial of EVX-01 has shown that 67% of nine patients benefitted from EVX-01 in combination with a PD-1 inhibitor (KEYTRUDA) for the treatment of metastatic melanoma, compared to the historical data of only 40% benefiting from a PD-1 inhibitor alone
●22% of the patients in the Phase 1/2a clinical trial achieved a complete response (full recovery) with EVX-01 in combination with a PD-1 inhibitor (KEYTRUDA).
●The first patient in the Phase 2b clinical trial has now been enrolled
●The Company anticipates interim topline data readout in H2 of 2023
●For further information, please refer to clinicaltrials.gov: KEYNOTE – D36 NCT05309421

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On September 21, 2022 Ensysce Biosciences, Inc. ("Ensysce" or the "Company") (NASDAQ:ENSC)(OTC PINK:ENSCW), a clinical-stage biotech company applying transformative chemistry to improve prescription drug safety to reduce abuse and overdose, reported that management will present during Benzinga’s All Access investor event taking place Friday, September 23, 2022 (Press release, Ensysce Biosciences, SEP 21, 2022, View Source [SID1234621294]).

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Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, is scheduled to host a presentation and Q&A session during the event as follows.

Benzinga All Access Event

Date: Friday, September 23, 2022
Time: 9:20 a.m. Eastern time
Webcast: View Source

A live video webcast will be available using the link above – an archived replay will be made available after the live event on the Benzinga YouTube Channel. For more information on Benzinga All Access, please contact your Benzinga representative.

On September 21, 2022 Coeptis Therapeutics, Inc. (the "Company" or "Coeptis") presented that posted an investor presentation (Presentation, Coeptis Pharmaceuticals, SEP 21, 2022, View Source [SID1234621293])

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