CLDN18.2 x TOP1

Swiss biotech Alentis Therapeutics thinks it can expand the reach of the Claudin family in oncology, and half a dozen new investors are helping back the idea with a $181.4 million Series D. Tuesday’s raise, which arrives 19 months after a $105 million Series C , will give the Basel-based biotech the chance to investigate the first anti-Claudin-1 ADC in human studies. The five-year-old biotech has already tested out the hypothesis with a monoclonal antibody in Phase 1. Now, it wants to see if the en vogue field of antibody-drug conjugates can also do the trick in treating CLDN1+ tumors. Part of a tight junction protein family known as Claudins, CLDN1 is known to play a role in shielding tumors from the immune system and driving organ disruption in fibrosis. Alentis CEO Roberto Iacone believes CLDN1 is implicated in nine “big indications” in cancer and could give the startup access to a broader patient population than other Claudin drugs, including the recently greenlit Claudin18.2 gastric cancer medicine from Astellas. “What we realize in the ADC space is that there is a scarcity of new targets,” Iacone told Endpoints News . “So essentially we belong to the new targets, Claudin-1, but at the same time, Claudin-1 is in a protein family space that is very well derisked.” The biotech plans to enter Phase 1 next quarter with a tubulin inhibitor-based ADC known as ALE.P02. The company will bring another anti-CLDN1+ ADC into the clinic next year as well. That second ADC is a topoisomerase 1 inhibitor and codenamed ALE.P03. Alentis also has a CLDN1-targeted monoclonal antibody in two clinical trials for fibrosis conditions . That asset, dubbed lixudebart or ALE.F02, has attracted big pharma interest because of the few mechanisms of action available in the organ fibrosis space, Iacone said. With a new board in place, the company will figure out next steps for that program, including potential partnerships, the CEO said. In conjunction with the Series D, Alentis added OrbiMed’s Dina Chaya, Frazier’s Anna Chen and Longitude’s Brian Liu to the board. Beyond those clinical programs, the 50-employee startup has a pipeline of other bispecific antibodies, ADCs and T cell engagers, a modality that has also caught the attention of multiple pharma acquirers and investors in recent months. With the new round and market conditions seemingly improving, Alentis could consider a Nasdaq listing as its next financial milestone, Iacone said. The company should have early data on its lead ADC within about 18 months, which will be “very important momentum for the company,” he added. The CEO also highlighted the M&A experience of Alentis’ board members, as many large pharmas have splashed billions of dollars on ADC consumptions in recent years. Alentis chair Luca Santarelli was CEO of VectivBio when Ironwood bought it and CEO of Therachon when Pfizer acquired it. Board director William Pao was chief development officer when Pfizer made the $43 billion bet on Seagen and its ADC pipeline. OrbiMed led the Series D. Novo Holdings and Jeito Capital co-led the round, which also included new investors Frazier Life Sciences, Longitude Capital, Catalio Capital Management and others.

Alentis Therapeutics already has two antibodies against CLDN1 in clinical testing, but the biotech is looking to build out its pipeline by turning one of the hottest modalities against the target — antibody-drug conjugates (ADCs). The company raised a $181.4-million D round on Tuesday to fund Phase I/II studies for a pair of CLDN1-targeting ADCs.The financing was led by OrbiMed and featured Novo Holdings — the controlling shareholder of Novo Nordisk — and Jeito Capital as co-leads. Since launching in 2019 with a $12.5-million A round, Alentis has raised more than $365 million, including a $67-million series B in 2021 and $105 million in series C funding.New investors Frazier Life Sciences, Longitude Capital, Catalio Capital, Piper Heartland Healthcare Capital and Avego Bioscience Capital also participated in the round, as did existing backers RA Capital Management, Morningside Venture Investments, BB Pureos, and Bpifrance through its InnoBio 2 fund.The capital injection comes less than a month after the FDA approved the first Claudin-targeting drug in the US: Astellas' anti-CLDN18.2 antibody Vyloy (zolbetuximab-clzb) for first-line gastric cancer. The Claudin family has quickly become the source of some of the most popular targets for solid tumour drug development, though efforts have mostly focussed on CLDN18.2 or CLDN6 with more than 30 assets in the clinic against the two targets, collectively. For further analysis on the Claudin landscape, see Spotlight On: New players emerge in anti-Claudin arena and Spotlight On: What’s next in the anti-Claudin pipeline?All in on ClaudinTuesday's financing will propel ALE.P02 and ALE.P03, both CLDN1-targeting ADCs, into Phase I/II testing for CLDN1-positive cancers. The most advanced, ALE.P02, carries a tubulin inhibitor and is expected to start its trial in patients with advanced or metastatic squamous solid tumours in the first quarter of 2025. ALE.P03, which has a topoisomerase I payload, is wrapping up GLP toxicity studies and is slated to enter the clinic next year.Alentis also has lixudebart (formerly ALE.F02), a monoclonal antibody (mAb) that targets exposed CLDN1 in fibrotic tissue, in a Phase II trial for kidney fibrosis and a Phase Ib study for liver fibrosis.The firm's other clinical-stage asset is ALE.C04, a CLDN1-targeting mAb in a Phase I/II study of patients with head and neck squamous cell carcinoma.

SAN FRANCISCO and SUZHOU, China, May 6, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI343 as monotherapy for the treatment of claudin18.2-positive advanced gastric/gastro-esophageal junction adenocarcinoma (GC) patients who have progressed after at least 2 lines of prior systematic treatments. The BTD for IBI343 was based on the data from an ongoing Phase 1 study (NCT05458219), in which favorable safety and tolerability and promising antitumor activity of IBI343 monotherapy in advanced GC patients were observed. The study results will be published at an upcoming medical conference later in 2024. Innovent is preparing for a registrational Phase 3 multi-regional clinical trial (MRCT) of IBI343 in patients with claudin18.2-positive, HER2-negative GC (G-HOPE-001, NCT06238843) to be initiated soon. Dr. Hui Zhou, Senior Vice President of Innovent, said, "GC patients tend to progress after second-line systematic therapies with poor prognosis and have only a half year of survival expectancy. They are in urgent need of effective third-line treatment options. We are glad to see the NMPA granted BTD for IBI343 monotherapy based on the PoC clinical results in GC, and we will continue to validate its efficacy and safety in the registrational MRCT trial. Innovent has a comprehensive and robust oncology pipeline, and, particularly in GC, we have PD-1 inhibitor (TYVYT®) for first-line GC treatment and anti-angiogenic drug (CYRAMZA®) for second-line GC treatment. We will further explore IBI343's potential in combination therapy as well as in other solid tumors such as pancreatic cancer." NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs that have been granted BTD by NMPA. About Gastric/ Gastroesophageal Junction Adenocarcinoma Gastric cancer is one of the most common malignant tumors in the world and is one of the leading causes of cancer-related deaths globally. The 5-year survival rate of patients with metastatic gastric cancer is less than 5%[i]. China and Japan are countries with highest incidence of gastric cancer[ii]. Currently, chemotherapy combination of fluoropyrimidine and platinum and immune checkpoint inhibitor therapy are the standard-of-care treatments for patients with advanced metastatic gastric cancer. However, systemic therapy has limited efficacy in advanced gastric cancer. In particular, the prognosis for patients with third-line or higher gastric cancer is usually poor, with fewer treatment options and shorter survival expectations. The median survival times for these patients is only about 0.5 year[iii]. Claudin, a member of the tight junction molecule family, is a key structural and functional component of epithelial tight junctions. Among them, CLDN18.2 is normally buried in the gastric mucosa, but the development of malignancy leads to disruption of tight junctions and exposure of CLDN18.2 epitopes on the membrane of tumor cells[iv]. CLDN18.2 is expressed in up to 80% of patients with gastric cancer. About IBI343 (Claudin18.2 ADC) IBI343 is an antibody-drug conjugate composed of an anti-claudin18.2 antibody, and a cytotoxic drug exatecan. As a topoisomerase I inhibitor, exatecan effectively kills tumor cells by inhibiting DNA synthesis. Binding of IBI343 to claudin18.2-expressing tumor cells results in claudin18.2-dependent internalization of IBI343. Degradation of the cleavable linker will release the drug that causes DNA damage, leading to apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring tumor cells, resulting in a strong "bystander killing effect" of IBI343. About Innovent Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 10 products in the market. It has 3 new drug applications under regulatory review, 5 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center. Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit , or follow Innovent on Facebook and LinkedIn. Note: TYVYT® (sintilimab injection) is not an approved product in the United States. BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States. TYVYT® (sintilimab injection, Innovent) BYVASDA® (bevacizumab biosimilar injection, Innovent) HALPRYZA® (rituximab biosimilar injection, Innovent) SULINNO® (adalimumab biosimilar injection, Innovent) Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan. CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China. Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s). Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions. Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. References: SOURCE Innovent Biologics