Novalgen Ltd.

- Patients with R/R CLL and MCL show good objective responses to ROR1-targeting T cell engager NVG-111 in combination and monotherapy settings - - Autoregulation (AR) platform displays significant protective effects from T cell engager toxicity and will enter the clinic with NVG-222 in 2024 - LONDON, Dec. 10, 2023 (GLOBE NEWSWIRE) -- NovalGen Ltd (“NovalGen”), a pioneering clinical stage immunology company, shared promising findings from the NVG-111-101, a First in Human, Phase I clinical study (NCT04763083), in an oral presentation at the 65th American Society of Hematology Annual meeting, in San Diego, USA. The study showcased positive responses in 58% of evaluable patients with relapsed refractory chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) across both combination and monotherapy regimens, durable to 24 months. Noteworthy outcomes include a remarkable achievement of MRD4 negativity in peripheral blood, determined by flow cytometry, in 30% of CLL participants. Furthermore, a complete metabolic response (CMR) by Lugano criteria was observed in one of two mantle cell lymphoma participants. Such outcomes are particularly significant in diseases characterized by poor T cell function and are associated with improved progression free survival and overall survival. Professor Amit Nathwani, Founder and CEO of NovalGen, expressed his enthusiasm for the results, stating, “The manageable safety profile together with encouraging clinical activity provide a strong foundation for ROR1 targeting T cells engagers and paves the way for their use in other hard to treat malignancies. including solid tumors.” Dr Jasani the Chief Investigator for this study stated: “Our pilot study shows the potential of ROR1 targeting T cell engagers in participants with CLL and MCL who have failed multiple lines of therapy including stem cell transplantation.” In addition to presenting these encouraging clinical outcomes, NovalGen is also introducing their proprietary Autoregulation (AR) technology platform. This innovative platform is showcased in the development of NVG-222, a next-generation T cell engager targeting ROR1 but can be applied to a range of immunotherapies including CAR-T cells to improve the therapeutic index. NVG-222 stands out with its extended half-life, enabling dosing once every two weeks. The enhanced safety profile of this novel molecule allows for higher, more efficacious dosing, potentially leading to improved patient outcomes. Professor Nathwani remarked, “By maintaining the potency of NVG-111 while extending half-life and significantly reducing mode-of-action-related toxicity, NVG-222 has the potential to extend the therapeutic window and set a new standard for patient care for ROR1 positive hematologic malignancies as well as solid tumors.” NovalGen believes that Autoregulation (AR) technology represents a transformative step in immunotherapy development, aiming to eliminate or reduce mode-of-action toxicities that limit the full potential of these new class of therapeutics leading to enhanced outcomes for patients. The company remains committed to advancing innovative solutions that address unmet medical needs and improve the lives of those affected by challenging diseases. Abstracts presented: Abstract Title: Time Limited Exposure to a ROR1 Targeting Bispecific T cell Engager (NVG-111) Leads to Durable Response in Subjects with Relapsed Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL)Link to AbstractSession Title: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: New Inhibitors and Cellular Therapies for Treatment of Relapsed CLLSession Date: Saturday, December 9, 2023Presentation Time: 4:00 PM - 5:30 PM PTLocation: Manchester Grand Hyatt San Diego, Grand Hall DPublication Number: 329Presenting Author: Dr Parag JasaniAbstract Title: NVG-222: A First-in-Class Autoregulating Half-Life Extended ROR1xCD3 T Cell Engager Heralding a New Class of Safer DrugsLink to AbstractSession Title: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster IISession Date: Sunday, December 10, 2023Presentation Time: 6:00 PM - 8:00 PM PTLocation: San Diego Convention Center, Halls G-HPublication Number: 2820Presenting Author: Dr Vincent Muczynski About NovalGen NovalGen is a privately held clinical stage immunology company developing breakthrough immunotherapies, with the aim of creating life-saving novel treatments for people with immunologically driven diseases. Our Autoregulation (AR) platform can be applied to multiple drug modalities for a wide range of indications in oncology, hematology, inflammation and other areas in the immunology space. Our dedicated team of experienced scientists, physicians and professionals are passionate about building a pipeline of disruptive and differentiated products tailored to the needs of the patient. The company’s lead program, NVG-111, is an ROR1-targeting bispecific antibody T-cell engager for the treatment of both hematological malignancies and solid tumors using our breakthrough bispecific antibody technology. Our lead AR programme, NVG-222, builds on the success of NVG-111 and is primed for entry into the clinic in 2024. About Autoregulation (AR) AR is NovalGen’s proprietary platform for next-generation therapeutics that has the potential to transform the treatment paradigm across multiple indications. AR therapies harness a response-mediated negative-feedback loop that detects when there is the risk of severe toxicities arising from the drug’s mechanism of action. When this occurs, the drug is deactivated at the site of action to prevent serious side effects. As the risk of toxicity reduces the drug is replenished from circulating active drug and treatment continues. AR enables the potential for therapies to be safely given at higher doses and for longer, widening the therapeutic index and resulting in better outcomes for patients. About Chronic Lymphocytic Leukemia (CLL) CLL is the most common form of leukemia in the Western world and is a type of cancer that affects a specific type of white blood cell called B-lymphocytes. These abnormal lymphocytes accumulate in the blood, bone marrow, lymph nodes, spleen and other tissues. Common symptoms of CLL can include fatigue, enlarged lymph nodes, and susceptibility to infections. However, not everyone with CLL will experience these symptoms. Treatment options for CLL can vary and may include watchful waiting, chemotherapy, immunotherapy, targeted therapy, or stem cell transplantation, depending on the individual's specific situation and stage of the disease. About Mantle Cell Lymphoma (MCL) MCL is an aggressive but rare cancer that affects white blood cell called B-lymphocytes located in the mantle zone the body's lymphatic system. Typical symptoms include swollen lymph nodes, fatigue, and digestive problems. It can be treated with different therapies, including chemotherapy, targeted drugs, and stem cell transplantation depending on the stage of disease and individual factors. Further informationJW CommunicationsJulia WilsonTel. +44 (0) 7818 430877Email: juliawilsonuk@gmail.com

- Updated clinical data for ROR1xCD3 targeting TCE NVG-111 in hematological malignancies focussed on relapsed / refractory CLL and MCL- - Pre-clinical data for NVG-222, a first-in-class half-life extended Autoregulated T Cell engager targeting ROR-1- LONDON, Nov. 02, 2023 (GLOBE NEWSWIRE) -- NovalGen Ltd (“NovalGen”), a biopharmaceutical company developing breakthrough immunotherapies, alongside an Autoregulation platform, today announces the online publication of two abstracts submitted to the American Society of Hematology Annual meeting, to be held December 9-12, 2023 in San Diego, USA. “We are pleased to announce our forthcoming oral presentation on the hematological arm of the NVG-111-01 Phase I clinical study (NCT04763083). Our comprehensive findings reveal highly favorable safety and efficacy outcomes among patients with relapsed/refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL), with patients demonstrating encouraging activity in both monotherapy and combination therapy groups. Building upon these achievements, we are advancing the development of NVG-111 into solid tumor indications,” said Professor Amit Nathwani, Founder and CEO of NovalGen. “We are also presenting a poster detailing the development of NVG-222, our next-generation T cell engager that will enter clinic in 2024 and carries our proprietary Autoregulation or ‘AR’ platform. NVG-222 unlocks the potential of AR in clinic with its ability to automatically deactivate when there is risk of toxicity at the site of action. This mitigates adverse events but also facilitates the administration of higher doses over extended durations, thereby expanding the therapeutic index. We firmly believe AR can be a paradigm-shifting development for a range of immunotherapies.” Oral Presentation: Abstract Title:Time Limited Exposure to a ROR1 Targeting Bispecific T cell Engager (NVG-111) Leads to Durable Response in Subjects with Relapsed Refractory Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL) Link to abstract Session Title: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: New Inhibitors and Cellular Therapies for Treatment of Relapsed CLL Session Date: Saturday, December 9, 2023 Presentation Time: 4:00 PM - 5:30 pm PT Location: Manchester Grand Hyatt San Diego, Grand Hall D Publication Number: 329 Presenting Author: Dr Parag Jasani Summary: Between May 2021 and July 2023 12 subjects (10 males and 2 females, median age 60 years) completed a maximum of 6 cycles of NVG-111 treatment, with all evaluable for toxicity and 11 evaluable for efficacy. Grade 1 or 2 CRS occurred in 58% of subjects, mainly in week 1 cycle 1. Objective clinical responses were observed in 55% of subjects, including two with clear evidence of single agent activity. Amongst these, three CLL subjects were rendered MRD negative in peripheral blood and one MCL subject achieved complete metabolic response by the Lugano criteria. These data provide clinical proof of concept for objective antitumor activity by ROR1 targeting TCE NVG-111, even in CLL patients known to have defective T cell function, with a safety pro with the mechanism of action. Further evaluation of this promising molecule is now progressing into solid tumors. Poster Presentation: Abstract Title:NVG-222: A First-in-Class Autoregulating Half-Life Extended ROR1xCD3 T Cell Engager Heralding a New Class of Safer Drugs Link to abstract Session Title: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II Session Date: Sunday, December 10, 2023 Presentation Time: 6:00 PM - 8:00 pm PT Location: San Diego Convention Center, Halls G-H Publication Number: 2820 Presenting Author: Dr Vincent Muczynski Summary: Building on the success of lead clinical programme of NVG-111, NovalGen’s proprietary Autoregulation (AR) platform has been applied to next-generation half-life extended T cell engager NVG-222. This groundbreaking technology aims to improve the safety pro extend the therapeutic window to improve patient outcomes. NovalGen have shown that applying AR to TCEs does not affect the potency, but significantly reduces toxicity in pre-clinical models. Furthermore, modelling from preclinical PK suggests NVG-222 will support dosing once every two weeks in clinic, and is due to enter trials in 2024. About NovalGen NovalGen is a privately held clinical stage immunology company developing breakthrough bispecific therapies, with the aim of creating life-saving new treatments for people with immunologically driven diseases. Our Autoregulation (AR) platform can be applied to multiple drug modalities for a wide range of indications in oncology, hematology, inflammation and other areas in the immunology space. Our dedicated team of experienced scientists, physicians and professionals are passionate about building a pipeline of disruptive and differentiated products tailored to the needs of the patient. The company’s lead program, NVG-111, is an ROR1-targeting bispecific antibody T-cell engager for the treatment of both hematological malignancies and solid tumors using our breakthrough bispecifics technology. Our lead AR programme, NVG-222, builds on the success of NVG-111 and is primed for entry into the clinic in 2024. About Autoregulation (AR) AR is NovalGen’s proprietary platform for next-generation therapeutics that has the potential to transform the treatment paradigm across multiple indications. AR therapies harness a response-mediated negative-feedback loop that detects when there is the risk of severe toxicities arising from the drug’s mechanism of action. When this occurs, the drug is deactivated at the site of action to prevent serious side effects. As the risk of toxicity reduces the drug is replenished from circulating active drug and treatment continues. AR enables the potential for therapies to be safely given at higher doses and for longer, widening the therapeutic index and resulting in better outcomes for patients. About Chronic Lymphocytic Leukemia (CLL) CLL is the most common form of leukemia in the Western world and is a type of cancer that affects a specific type of white blood cell called B-lymphocytes. These abnormal lymphocytes accumulate in the blood, bone marrow, lymph nodes, spleen and other tissues. Common symptoms of CLL can include fatigue, enlarged lymph nodes, and susceptibility to infections. However, not everyone with CLL will experience these symptoms. Treatment options for CLL can vary and may include watchful waiting, chemotherapy, immunotherapy, targeted therapy, or stem cell transplantation, depending on the individual's specific situation and stage of the disease. About Mantle Cell Lymphoma (MCL) MCL is an aggressive but rare cancer that affects white blood cell called B-lymphocytes located in the mantle zone the body's lymphatic system. Typical symptoms include swollen lymph nodes, fatigue, and digestive problems. It can be treated with different therapies, including chemotherapy, targeted drugs, and stem cell transplantation depending on the stage of disease and individual factors. Further information JW Communications Julia Wilson Tel. +44 (0) 7818 430877 Email: juliawilsonuk@gmail.com

None  Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week.  FDA's Peter Marks has no "imminent plans for departure" Center for Biologics Evaluation and Research Peter Marks, M.D., Ph.D., was forthright but understated when describing the last few years leading the FDA’s Center for Biologics Evaluation and Research, calling the period “challenging,” in an interview. But like any good high-ranking public servant, he dolloped on some positive spin, describing a moment defined by COVID, former President Donald Trump, turnover, stress, scrutiny, variants and remote work as an “incredible learning experience.”  Nobody is losing sleep because a really high-profile figure had to deal with a lot. But suffice to say, Marks has had plenty on his plate running an FDA center that oversees the approval of new cell and gene therapies and neurological products, among other responsibilities. And for now, he’s pressing ahead, saying he has no plans to step away.  “Am I going to be doing this forever? Probably not,” Marks said. “On the other hand, I don't have any imminent plans for departure, in part because every day I wake up and there's some new, interesting thing to help move forward.” He added that so long as he feels like his contribution is benefiting patients, he’ll stay on. But the 11-year veteran on the agency had a caveat, one that’s been informed by his growing number of years around politicians, saying that he knows “to not be too definitive about these kinds of things.” UAB infectious disease division head Jeanne Marrazzo tapped to replace Anthony Fauci National Institute of Allergy and Infectious Diseases Hear ye, hear ye, a formal successor to Anthony Fauci, M.D., has been named!  Months after the longtime public health official stepped down from his post leading the National Institutes of Health's (NIH’s) infectious disease division, NIH interim chief Lawrence Tabak, Ph.D., has named Jeanne Marrazzo, M.D., as the new leader. Marrazzo is currently the head of the infectious disease division at the University of Alabama at Birmingham and is expected to join in the fall. Longevity in leadership positions within government seem like a rarity these days, as politician and polarization cripple once non-partisan posts. But Fauci was an outlier, serving 38 years as the director of National Institute of Allergy and Infectious Diseases, a tenure that spanned seven presidents, Republican and Democrat alike. But his biggest test would be his last, grappling with the rise and spread of COVID-19, advocating for mitigation policies that ultimately became a line in the sand for millions of Americans, largely on party lines. Fauci also became President Joe Biden’s chief medical adviser before retiring at the end of 2022.  Marrazzo’s research has centered on the human microbiome and how it impacts female reproductive tract infections and hormonal birth control, according to a release from the NIH, in addition to studying other sexually transmitted infections. She’s been a principal investigator on NIH grants for more than 25 years and was the presented with the American Sexually Transmitted Diseases Association’s Distinguished Career Award in 2022. Release Former EQRx finance chief takes same role at Boundless Boundless Bio Jami Rubin’s two-month stint as a venture partner at ARCH is caput after the former EQRx CFO took the same role at San Diego biotech Boundless Bio. Let’s hope for her sake that she was able to make it up to Absolute Bagels off 108th Street or a slice of pizza at John’s on Bleeker during her return to New York City. (She spent years there before jumping to biotech.) Rubin left EQRx in March 2023, right around the time that the company instituted a first round of layoffs resulting in cuts to 18% of the team. But it turns out that was only the beginning of a major overhaul for the Alexis Borisy-founded company. A couple of months later, another round of layoffs sent more than half of the company out the door, along with EQRx’s larger strategy of producing low-cost cancer treatments. This week EQRx announced it was being sold to announcer Borisy biotech, Revolution Medicines.  It’s unknown whether Rubin saw the writing on the wall in March or whether the timing of her departure was sheer luck. But regardless, she’s onto greener pastures. Boundless is similarly focused on treating cancer, with a particular emphasis on oncogene-amplified tumors. And while EQRx was shrinking, Boundless was raising new cash, closing another nine-digit round in May. Source > OMass Therapeutics has appointed Peter Phillips, M.D., Ph.D., to the job of SVP of clinical development and Julia Sampson, Ph.D., to serve as VP of nonclinical development. Before filling the newly created positions, Phillips was at Evelo Biosciences and has a track record at NovalGen, UCB, GSK, Novartis and Pfizer, while Sampson has worked across Kalvista Pharmaceuticals, AstraZeneca, Shire Pharmaceuticals, OSI Pharmaceuticals and GW Pharmaceuticals. Release > Catena Biosciences is bringing on two new leaders for its executive team: Saurabh Johri to serve as chief business officer and Rick Kendall, Ph.D., to fill the role of chief scientific officer. Johri joins from Bayer, where he most recently was VP and global head of oncology strategy and early commercialization, while Kendall was most recently president and CEO of ImmPACT BIO, clocking in time before that at Kite Pharma and Amgen. Release > ImmunoGen Chief Medical Officer and SVP Anna Berkenblit, M.D., is exiting the company for a “professional hiatus” before pursuing new opportunities outside of ImmunoGen. Berkenblit will leave at the end of August, and Michael Vasconcelles, M.D., ImmunoGen EVP of R&D and medical affairs, will take on the CMO role. Release > TheracosBio CEO Albert Collinson, Ph.D., is handing the reins over to newcomer Brian Connelly. The new leader has practiced law for over 15 years for a law firm supporting biotech and life science companies and also co-founded IncreVet, a veterinary drug development company acquired by Theracos—TheracosBio’s parent company—last year. Release > Incyte’s chief scientific officer Dashyant Dhanak, Ph.D., has left the pharma to pursue other opportunities. Dhanak has held the CSO position since 2018, overseeing more than 15 investigational new drug applications—or requests to bring a drug into the clinic—during that time. Release > Zentalis Pharmaceuticals is welcoming Kimberly Freeman on as chief strategy officer. Before Zentalis, Freeman was VP, U.S. head of DDR franchise, oncology at AstraZeneca and has previously held leadership roles at Adaptimmune, Boehringer Ingelheim and GSK. Release > Ambrx Biopharma has snagged Renu Vaish to serve as the company’s chief regulatory officer. She most recently was SVP of regulatory affairs for SpringWorks and has held leadership roles at Celgene, Merck & Co. and Kite Pharma. Release > Viral-disease-focused Bioxytran has tapped Leslie Ajayi, M.D., Ph.D., to serve in its newly created interim chief medical officer position as well as chief of the medical advisory board. Ajayi’s clinical research efforts have resulted in the creation of a number of technical reports for Big Pharmas like Merck & Co., Servier, Bristol Myers Squibb, Roche, Pfizer and GSK. Release > The National Pharmaceutical Council has added former Institute for Clinical and Economic Review executive Jonathan Campbell, Ph.D., as chief science officer to direct the group’s research portfolio. Release > Numerof & Associates has brought on former Bristol Myers Squibb, Amgen senior executive Michael Ryan as an executive adviser. He will help advise pharmaceutical clients at the healthcare strategy firm with strategy and planning, market access, policy analysis and other issues. Release > Former AdaptImmune executive Jeanette Evans will takeover as chief business officer of the Cell and Gene Therapy Catapult. The independent, U.K.-based organization works to advance cell and gene therapies through development. Release > Playground Global is bringing on a16z vet Nate Chang to expand its life science venture capital footprint. Chang spent nearly 15 years in healthcare investment banking before joining a16z in 2019. Release > Parisa Zamiri, M.D., is joining Complement Therapeutics as chief medical officer, jumping from Graybug Vision where she held the same role. Before Graybug, Zamiri was the ophthalmology therapeutic head at Novartis. Release > Numerous executive changes are afoot at Molecular Templates six weeks after another round of layoffs. Gabriela Gruia, M.D., has been named interim chief medical officer, Jason Kim will be president and chief financial officer, Kristen Quigly is the new chief operating officer and Grace Kim is now chief strategy officer and head of investor relations. Release