CELL AND GENE THERAPY
Vaderis Therapeutics AG | August 22, 2022
Vaderis Therapeutics AG a clinical stage biotechnology company focused on developing treatments for rare diseases associated with vascular malformations, today announced its emergence from stealth and initiation of its INSIGHT proof-of-concept clinical trial in patients suffering from Hereditary Haemorrhagic Telangiectasia also known as Osler-Weber-Rendu Syndrome. Vaderis was established in 2019 and in 2020 raised over CHF18 million from Medicxi, enabling progression of its lead asset into the clinic and successful completion of Phase 1a.
Emergence from Stealth
Vaderis was founded with the unique aim to develop therapeutics for rare and orphan diseases associated with vascular malformations. In April 2020 Vaderis acquired a portfolio of allosteric AKT inhibitors from Almac Discovery Ltd of Belfast, UK. AKT is a serine kinase which plays a crucial role in vascular growth and in vascular overgrowth. There is a significant number of rare diseases such as HHT in which upstream genetic mutations trigger over-activation of the serine kinase AKT, resulting in vascular overgrowth. Such diseases frequently manifest in ways that are debilitating, disfiguring, painful and sometimes life-threatening. The vast majority of these diseases are currently left untreated except for symptomatic interventions which tend to offer patients limited temporary relief of individual symptoms. VAD044 is a once daily, orally administered, allosteric AKT inhibitor which has the potential to treat the underlying cause of these diseases. If successful, Vaderis would be the first company in the world to develop a medicine for the treatment of HHT and other diseases associated with vascular malformations.
Initiation of Clinical PoC in HHT
In pursuit of the company's core objective, Vaderis announces the initiation of the first study of VAD044 in HHT patients. Known as the INSIGHT proof-of-concept trial (INternational Study InvestiGating HHT), the study is unique in its robust design aimed at achieving a thorough understanding of the safety of VAD044 in HHT patients. A total of 80 HHT patients across the USA, Canada and Europe will be randomised in a double-blind, controlled trial comparing two doses of VAD044 to placebo. Initiation of the INSIGHT trial follows Health Authority approvals including FDA, Health Canada and key European agencies.
J.J. Mager, MD, PhD, pulmonologist at St. Antonius Hospital Utrecht, Chairman of the Global Research and Medical Advisory Board of Cure HHT and lead investigator of the INSIGHT trial commented, "The first patients recruited into the INSIGHT trial mark an exciting milestone in HHT clinical research. If successful, this trial may demonstrate the potential of this new drug to be effective beyond the symptomatic treatments we currently offer HHT patients, by addressing the course of this rare, progressive, and debilitating disease."
"Working together with the HHT community, both caregivers and patient associations, Vaderis hopes to be the catalyst which transforms patient care in HHT. Success in the INSIGHT trial would be a major step towards developing the first ever registered treatment for HHT anywhere in the world."
Nicholas Benedict, CEO of Vaderis
Giovanni Mariggi, Partner at Medicxi and Chairman of Vaderis said, "Our vision is to create a unique company dedicated to delivering breakthrough therapies for rare diseases caused by vascular malformations. Initiation of the INSIGHT trial is an important milestone on the way to realising this vision. It is testament to the significant progress made by the company over the last two years".
Vaderis is a clinical stage biotech company with the aim to develop medicinal treatments for rare and orphan diseases associated with vascular malformations. Since its founding in 2019, Vaderis raised a Series A financing from Medicxi and acquired a portfolio of allosteric AKT inhibitors from Almac Discovery Ltd of Belfast, UK. There is a significant number of debilitating and largely untreated rare diseases, such as HHT (Hereditary Haemorrhagic Telangiectasia), in which patients suffer from over-activation of AKT triggered by upstream genetic mutations resulting in vascular overgrowth. There are no drugs approved anywhere in the world which specifically treat HHT. Vaderis aims to be the first company to develop a medicine for the treatment of HHT and aims to treat other diseases associated with vascular malformations.
Medicxi is a healthcare-focused investment firm with the mission to create and invest in companies across the full drug development continuum. Leveraging deep expertise in drug development and company creation spanning over two decades, Medicxi invests in early and late-stage therapeutics with a product vision that can fulfill a clear unmet medical need.
Novaliq GmbH | August 10, 2022
Novaliq, a biopharmaceutical company focusing on first- and best-in-class ocular therapeutics based on the unique EyeSol® water-free technology, announced the submission of a New Drug Application to the U.S. Food and Drug Administration seeking approval for CyclASol® a proposed novel treatment for the signs and symptoms of dry eye disease.
CyclASol® has demonstrated in two pivotal studies fast onset of therapeutic effect in the indication, clinical meaningful improvement of ocular surface damage, and excellent tolerability. Results from a 12-month long-term study confirmed that the effects are maintained, and even improved for most sign and symptom endpoints.
"This is the first submission of a novel product category of water-free topical drug therapies utilizing EyeSol® as a drug carrier. CyclASol® is a first-of-a-kind drug therapy and aims to expand treatment success for patients with dry eye disease and their eye care professionals. If approved by the FDA, CyclASol® addresses important unmet medical needs in DED through its ocular surface healing effect combined with high comfort of administration."
Christian Roesky, Ph.D., CEO, Novaliq
Dry eye is one of the most common ocular surface disorders, with approximately 18 million Americans diagnosed with DED.1,2 Inflammation and immunologic processes play a key role in the pathology of the disease.
A compromised ocular surface secondary to DED may also compromise refractive measurements before keratorefractive and phacorefractive surgeries and adversely impact expected visual outcomes after these surgeries.3,4 The impact of the corneal surface damage secondary to DED on visual function is an underestimated aspect of the disease. Multiple guidelines recommend treatment of the corneal surface damage prior to ocular procedures. A high unmet need remains for better tolerated drugs with an early onset of therapeutic effect, which are compelling to be used and prescribed.5,6
"We are very proud to see another product rapidly moving to the market, which marks yet another important inflection point and milestone in Novaliq's growth trajectory", said Dr. Mathias Hothum, board member and managing director of dievini. "We are currently evaluating the commercialization strategies which includes talking to interested parties."
CyclASol® is a first-of-a-kind topical treatment of cyclosporine, a potent anti-inflammatory and selective immunomodulatory drug. Whilst not water-soluble, cyclosporine is soluble in the EyeSol® excipient perfluorobutylpentane allowing for its improved bioavailability and better efficacy on the target tissue. The product contains no oils, no surfactants and is preservative-free due to the novel carrier. This provides additional clinical benefits for patients, such as improved tolerability and decreased visual disturbances.
The NDA is supported by safety and efficacy results in over 1,000 patients with DED from a Phase 2 dose finding study, the Phase 2b/3 ESSENCE-1 study, the Phase 3 ESSENCE-2 study and its open label extension study.7,8
CyclASol® has demonstrated in two independent adequate and well-controlled, multicenter studies clinically meaningful and statistically significant improvements in the indication.
Effects on the ocular surface include a statistically significant reduction in total corneal fluorescein staining score favoring CyclASol® in both studies at Days 15 and 29. Up to 71.6% of patients responded within four weeks with a clinically meaningful improvement of ≥ 3 grades in total corneal staining. This proportion of responders was significantly higher compared to vehicle-treated patients in both studies. Responders showed also statistically significant improvements in a variety of symptoms compared to non-responders at day 29. The ASCRS guidelines recognize corneal staining as the single most important clinical sign of DED as it indicates the level of epithelial damage and visual impairment, and if left undertreated, DED can become chronic and more difficult to treat.3
Effect on tear production: In both studies, compared to vehicle at the end of treatment, there was a statistically significant (p<0.05) higher percentage of patients with increases of ≥ 10 mm from baseline in Schirmer's tear test score at Day 85 and Day 29, respectively, confirming a known effect of the active ingredient cyclosporine. Meeting this endpoint in two independent studies is clinically meaningful on its own and considered to demonstrate efficacy for the treatment of signs and symptoms of DED.
Head-to-head data versus Restasis™ from the phase 2 study suggest that CyclASol® has a stronger and faster therapeutic effect on the ocular surface.8
Maintenance of effect results from the long-term study CYS-005 confirmed that the effect of CyclASol® was maintained, and even improved for most endpoints, over the 52-week treatment period.
Safety and Tolerability: Tolerability of CyclASol® was shown by high drop comfort patient ratings in both studies. The most common adverse reaction observed was instillation site reactions, which was reported in 8.1% of patients in the pooled studies. These were in all but one case mild. The only other adverse reaction reported in > 2% of the patients was visual acuity reduced (2.7%).
Novaliq is a biopharmaceutical company focusing on the development and commercialization of first- and best-in-class ocular therapeutics based on EyeSol®, the worldwide first water-free technology.
EyeSol® is Novaliq's proprietary water-free technology using ultrapure semifluorinated alkanes (SFAs) that are physically, chemically, and physiologically inert with excellent biocompatibility and a very good safety profile. Novaliq offers an industry-leading portfolio addressing today's unmet medical needs of millions of patients with eye diseases.
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.