Convergent Therapeutics, Inc.

Taylor Tieden for BioSpace Pharmaceutical companies are combining antibodies with radioisotopes in a bid to more precisely deliver radiation to cancers and tumors. Radiation treatments for cancer often come with side effects like fatigue, hair loss, nausea and skin irritation because as the waves traverse through the body, they affect all the cells they pass on the way to the cancer cells. Despite this, radiation is still used because it is simply good at treating certain cancers. However, several companies are looking to radiolabeled antibody-drug conjugates (rADCs) to bypass these side effects and deliver radiation only to cancer cells without affecting healthy ones, speed up treatment times and enable lower doses than traditional therapies. “We’re still in a position where there have been only two radiotherapeutics approved right now in this renaissance of radiopharmaceuticals,” said Lana Janes, co-founder and chief operating officer of rADC developer Abdera. Those two are Novartis’ Pluvicto and Lutathera , radiolabeled small molecules that were approved to treat specific types of prostate cancer and neuroendocrine tumor, respectively. Keen to fill this gap, Big Pharma is dropping billions to gobble up biotechs with early-stage radiopharma assets, while still other companies are advancing clinical development of rADCs, a category of radioimmunotherapies that has yet to see its first FDA approval. ADCs have been tested as cancer therapeutics for decades, spurred by the magic bullet concept proposed in the early 1900s. ADCs are essentially antibodies tethered to a drug of choice, in this case radioisotopes. “The future of ADCs is actually experimenting with novel payloads,” said Chris Bardon, a co-managing partner of MPM BioImpact. Bound by chelators, the radioisotopes home in on cancer or tumor cells thanks to antibodies, which attach to receptors on the cell surface. Once absorbed by the cells, the radioisotopes are released from the chelators and are free to exert their destructive powers. By releasing the radioisotope only in the target cells and nowhere else, drug developers hope that rADCs will markedly ameliorate the side effects associated with traditional radiotherapy and hasten treatment. The first radioimmunotherapies for cancer treatment were approved in the early 2000s for non-Hodgkins lymphoma, but were not preferred over existing chemotherapy regimens. Since then, however, many rADCs bearing actinium, lutetium and iodine isotopes, among others, have been developed and tested in clinical trials. Companies working on these drugs include Telix Pharmaceuticals, Actinium Pharmaceuticals, Convergent Therapeutics, Abdera Therapeutics, Bayer and Fusion Pharmaceuticals, all of which are advancing clinical-stage rADC candidates in conditions like prostate and breast cancer. “We really see this as an emerging modality that’s in the armament of an oncologist’s toolbox,” Janes said. Treating Cancers with rADCs Last year, Telix began a Phase III trial to assess the risks and benefits of its leading 177 lutetium-labelled ADC candidate for metastatic castration-resistant prostate cancer. A second is in the works. The drug, called TLX591, has an antibody that targets prostate-specific membrane antigen (PSMA), a marker of prostate cancer cells. By bringing radioactive lutetium directly to the cancer cells, TLX591 has been shown in interim Phase I results to reduce levels of prostate-specific antigen (PSA) in patients, an indicator of anticancer activity. The Phase III trials are set to wrap up in 2028, and Telix has other candidates in the pipeline for metastatic kidney cancer ( 177 Lu), glioblastoma ( 131 iodine) and bone marrow conditioning ( 90 yttrium). The antibody that eventually became part of TLX591 was first made by Neil Bander, an emeritus professor of urology at Weill Cornell University and one of the founders of Convergent Therapeutics, another prominent player in the rADC field. Convergent’s own lutetium-based prostate cancer candidate, CONV01-α, also reduced PSA levels in Phase I/II trials. CONV01-α uses the same antibody as TLX591, although Telix claims to have modified its version, said Shankar Vallabhajosula, vice president of radiopharmaceutical sciences at Convergent and emeritus professor of radiochemistry and radiopharmacy at Weill Cornell. Vallabhajosula was part of the initial efforts to figure out the therapeutic potential of the antibody beginning in the late 1990s. Having been in the field of radiochemistry for nearly 50 years, Vallabhajosula appreciates the precision of today’s drugs, which can be quantified down to the number of radioactive atoms per unit of antibody. This precision, alongside a readily available and well-characterized bank of chelating agents, has fueled the surge in rADCs, he said. Taking a different tack is Abdera Therapeutics, which has developed a platform for making custom antibodies that carry a desired payload. A key concern that comes with using biologics is optimizing the half-life of the targeting molecule, which can be tricky, said Janes. If a drug hangs around in the body for too long, it can cause problems like bone marrow toxicity and kidney load. But if it degrades too quickly, it may not kill enough tumor cells. To solve this puzzle, Abdera developed a platform called ROVEr that fine-tunes an antibody’s pharmacokinetics. Then, using a prepared library of linkers and chelators, the radioactive payload can be attached. By tweaking the biologic and pairing it with the right radioactive isotope, Abdera hopes to “get enough of those individual [radioactive] particles releasing inside of the tumor without them also decaying and being released near the healthy tissue,” Janes explained. Its lead candidate, a 225 actinium-loaded biologic called ABD-147, was recently granted orphan drug designation by the FDA and will be tested in Phase I trials for small cell lung cancer and large cell neuroendocrine carcinoma. Overcoming Supply and Delivery Hurdles Despite the precision and promise of rADCs, working with radioactive materials comes with unique challenges. A key issue is ensuring a steady and reliable supply of radioactive material, which is a problem given usually short half-lives that range from days (actinium) to mere hours (lead). As a result of this time constraint, radioisotopes are either made or sourced on demand and cannot be stored for long even after conjugating them with the antibodies, Janes explained. She is optimistic, however, that capacities will increase as more clinical trials are approved. “The number of contract manufacturers who are able to manufacture these drugs and provide them to clinical sites in time has increased, as well as the number of contract research organizations that are capable of working with these kinds of hot products,” Janes told BioSpace . Once an rADC is made, there is the matter of clinical trials and regulatory approvals. The FDA has a well-established pipeline for radiotherapeutic agents but often requires human dosimetry informationto understand how much radiation is absorbed in various tissues of the body, Vallabhajosula said, nothing that results from animal models may not translate to people. “Patients are not comfortable if you use them as guinea pigs just for dosimetry purposes,” he said. On the patient end, an enduring challenge has been the attrition rate of an ADC once it enters the body. Notwithstanding decades of engineering and fine-tuning of antibodies, chelators and linkers, no more than 2–3% of an injected ADC reaches the target tissue, Vallabhajousula said. Bardon stressed this issue, cautioning, “That’s part of the problem of picking winners before we generate clinical data.” Even so, patients are responding to experimental treatments and companies are forging ahead. “The clinical data is telling us things are working, producing the therapeutic effect, and the toxicity is not outrageous. That’s what is giving the hope,” Vallabhajosula said. Complemented by platforms from companies like Abdera and Actinium Pharmaceuticals, researchers can be hopeful of overcoming old obstacles, Janes said. “We’re all rooting for each other’s success.”

First Patient Dosed with CONV01-α in Phase II Clinical Trial in Patients with Metastatic Castration Resistant Prostate Cancer Drug Development Veteran Richard Messmann, MD Appointed as Chief Medical Officer to Lead the Development of CONV01-α Novo Holdings Invests $40 million in Series A Extension to Advance Clinical Development of Radiopharmaceuticals at Convergent Therapeutics CAMBRIDGE, Mass., Sept. 24, 2024 /PRNewswire/ -- Convergent Therapeutics Inc., a clinical stage biotechnology company focused on developing next generation radiopharmaceutical therapies for the treatment of prostate cancer and other cancers, today announced that the first patient has been dosed with CONV01-α in the Phase II CONVERGE-01 trial evaluating CONV01-α, Ac-225 rosopatamab tetraxetan, for the treatment of patients with prostate-specific membrane antigen (PSMA) PET-positive metastatic castration resistant prostate cancer (mCRPC). Previously conducted academic studies of CONV01-α have shown encouraging therapeutic results in patients with prostate cancer. According to Neil Bander, MD, Convergent's Co-founder and CSO, "In patients treated at Weill Cornell Medicine, CONV01-α demonstrated a prostate-specific antigen decline of 50% (PSA50) in 67% of patients and a PSA decline of 90% (PSA90) in 27% of patients." These results have prompted initiation of the CONVERGE-01 trial under Convergent's own Investigational New Drug License (IND). "We look forward to evaluating the full potential of CONV01-α and advancing the Phase II trial in the months ahead." The CONVERGE-01 trial is a Phase II, randomized, open-label, multicenter three-part study designed to assess the safety and efficacy of CONV01-α in patients with mCRPC. In Part 1, the first 5 participants will receive In-111-rosopatamab tetraxetan to characterize the biodistribution of the radioantibody to target organs and prostate cancer lesions. Participants will then be enrolled in either Part 2 (dose optimization) or Part 3 (dose escalation) depending on their prior treatment history. Part 2 will enroll Lu-177-PSMA-radioligand therapy-naïve participants and Part 3 will enroll participants who received prior Lu-177-PSMA-radioligand therapy. All patients will receive Ac-225 rosopatamab tetraxetan in a single fractionated two-week cycle. Further details of the trial can be found at under NCT identifier: NCT06549465. Chief Medical Officer Appointment Convergent announced that Richard Messmann, MD, MHS, MSc, has joined the company as Chief Medical Officer. Dr. Messmann is a medical oncologist and biochemist with over 25 years of experience in oncology drug development, including responsibility for the global clinical development and successful regulatory submission of Pluvicto® and Locametz® for the treatment of men with PSMA-expressing, mCRPC. Dr. Messmann has held leadership positions at Endocyte, Advanced Accelerator Applications (a subsidiary of Novartis), Fusion Pharmaceuticals, Amgen, Eli Lilly & Co., and others. Immediately prior to joining Convergent Therapeutics, Dr. Messmann was the Senior Vice President and clinical lead for Fusion's development of the actinium radiotherapeutic FPI-2265. While at Amgen, he was the executive medical director and global program lead for the development of xaluritamig (AMG 509) in prostate cancer. "We are excited to welcome Dr. Messmann to the Convergent team as we expand our clinical program for CONV01-α," said Convergent's Co-founder and CEO, Philip Kantoff, MD. "His deep knowledge and experience in oncology drug development, specifically leading the late-stage development of radiopharmaceuticals, is an important addition to our team as we look forward to progressing this asset forward." Series A Extension Funding Convergent announced a $40 million Series A extension by Novo Holdings, a holding and investment company wholly owned by the Novo Nordisk Foundation. This additional funding increases the total Series A raise to $130 million to support the development of Convergent's radiopharmaceutical pipeline, including CONV01-α. Jim Trenkle, PhD, Partner in the Venture Investments group at Novo Holdings, joins the Convergent Board of Directors. About CONV01-α CONV01-α, Convergent's alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeting prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called 225Ac, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers. About Convergent Therapeutics, Inc. Convergent Therapeutics Inc. is a clinical-stage biotechnology company focused on developing tumor-selective alpha radioantibodies to target cancer. The company was founded by world-renowned experts in clinical care and research, drug development and cancer biology and its proprietary platform is licensed from Cornell University. In harnessing the selectivity of antibodies and tumor-destructive potential of alpha radioisotopes, Convergent's radioantibodies precisely target cancer cells with potent, localized radiation. For more information, please visit and follow us on Twitter and LinkedIn. Media Relations: Bryan Blatstein Spectrum Science 917-714-2609 [email protected] SOURCE Convergent Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

BELOIT, WI & CAMBRIDGE, MA, USA I NorthStar Medical Radioisotopes , LLC, a global innovator in the development, production, and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, and Convergent Therapeutics , Inc., a clinical stage radiopharmaceutical company, today announced the signing of a strategic contract manufacturing services agreement. Convergent’s lead asset CONV01-α is a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody linked to Ac-225 and is currently being investigated as a treatment for prostate cancer. Under the terms of the expanded collaboration, NorthStar will: In March of this year, Convergent received U.S. Food and Drug Administration (“FDA”) clearance for its investigational new drug (“IND”) application for CONV01-α, a key milestone that enables Convergent to advance CONV01-α into Phase 2 studies and expand the scope of clinical development of CONV01-α as a monotherapy and in combination with other cancer therapies. The manufacturing supply agreement announced today will support these trials and, if U.S. FDA approved, the manufacturing of CONV01-α for commercial purposes. “The last several years have seen an explosion of research and clinical trials in the area of radiotherapies, especially those using Ac-225,” said Frank Scholz, Chief Executive Officer of NorthStar , “and yet today there are still far too few effective therapies for patients suffering from a variety of serious diseases including many cancers. Why? Because the processes to develop, manufacture and deliver therapeutically effective radiopharmaceuticals like Convergent’s CONV01-α to market – in particular at a scale able to meet patient demand for an approved, marketed medicine — are highly specialized and complex. At NorthStar, our passion is to reduce technological and operational barriers to help companies like Convergent Therapeutics not only secure a reliable source of Ac-225, but manufacture a finished, patient-ready drug product and continue to develop new and additional therapeutic indications for the patients who need new and better medicines. We are proud to be supporting Convergent and look forward to working with them to help make new medicines like CONV01-α therapeutic reality.” “We are excited to expand our partnership with NorthStar and the opportunity to leverage NorthStar’s unique position to scale both Ac-225 generation and manufacturing capacity,” said Caitlyn Harvey, Head of Manufacturing at Convergent . “Convergent will begin enrolling patients into the CONVERGE-01 Phase 2 clinical trial in the next couple of months as we continue building on extensive clinical experience which will allow us to rapidly move into our Phase 3 study.” About CONV01-α CONV01-α, Convergent’s alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeted at prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called Ac-225, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers. About Convergent Therapeutics, Inc. Convergent Therapeutics Inc. is a clinical-stage biotechnology company focused on developing tumor-selective alpha radioantibodies to target cancer. The company was founded by world-renowned experts in clinical care and research, drug development and cancer biology and its proprietary platform is licensed from Cornell University. In harnessing the selectivity of antibodies and tumor-destructive potential of alpha radioisotopes, Convergent’s radioantibodies precisely target cancer cells with potent, localized radiation. For more information, please visit www.convergentrx.com and follow us on Twitter and LinkedIn . About NorthStar Medical Radioisotopes, LLC (NorthStar) NorthStar Medical Radioisotopes is a commercial-stage radiopharmaceutical company at the forefront of advancing patient care by utilizing novel technologies to produce commercial-scale radioisotopes that, once attached to a molecule, have the ability to detect and treat cancer and other serious diseases. NorthStar’s expanding industry-leading position in the emerging field of radiopharmaceutical therapy is supported by its unique capabilities in the sophisticated production of radioisotopes, proven management team, and state-of-the-art, environmentally preferable technologies. NorthStar routinely produces copper-67 (Cu-67) and is poised to be the first commercial-scale producer of non-carrier-added (n.c.a.) actinium-225 (Ac-225). The Company’s Radiopharmaceutical Contract Development and Manufacturing Organization (CDMO) services unit provides customized service offerings and specialized radiopharmaceutical expertise to help biopharmaceutical companies rapidly advance their development and commercial programs. For more information about NorthStar’s comprehensive portfolio and patient-focused services, visit: www.northstarnm.com . SOURCE: NorthStar Medical Radioisotopes