Tislelizumab

New trial arm to evaluate safety, dosing and preliminary anti-tumor activity in advanced solid tumors March 18, 2025 -- Indaptus Therapeutics, Inc. (Nasdaq: INDP), a clinical-stage biotechnology company dedicated to developing novel treatments for cancer and viral infections, today announced that it has advanced to a new expansion arm of its Phase 1b/2 clinical trial of Decoy20. This expansion will evaluate the combination of Decoy20 with BeiGene’s PD-1 checkpoint inhibitor, tislelizumab, with a focus on safety, dose optimization, and early signs of anti-tumor activity. Jeffrey Meckler, CEO of Indaptus, commented, “This marks a pivotal step forward for Indaptus and our Decoy platform. Preclinical research has consistently shown that Decoy20 works synergistically with a checkpoint inhibitor, and we now have the opportunity to test that in patients for the first time. While this initial phase will focus on safety and tolerability, we are laying the groundwork for what could be a game-changing approach to treating solid tumors. This combination trial is not just a milestone – it’s an opportunity to showcase our platform’s versatility and move one step closer to improving patient outcomes.” Checkpoint inhibitors such as tislelizumab have improved outcomes in a variety of cancers but many patients still do not respond or ultimately do not experience a long-lasting effect. Decoy20 is engineered to activate the immune system in a manner that is theorized to significantly enhance and broaden the effectiveness of checkpoint inhibitors. Initial participants will first receive one week of Decoy20 monotherapy intravenously before starting the combination treatment with Decoy20 + tislelizumab. The first few patients in the combination phase will be enrolled sequentially to monitor safety. After review by the trial’s Safety Review Committee, unrestricted enrollment will begin. Participants will receive both treatments for up to one year, or until disease progression, unacceptable toxicity, or withdrawal from the study. PD-1 inhibitors work by blocking the PD-1 (programmed death-1) receptor on T cells, preventing cancer cells from evading the immune system and restoring the body’s ability to fight cancer. Combining checkpoint inhibitors with immune system activators like Decoy20 could provide a more powerful and sustained anti-tumor response. Indaptus is committed to advancing innovative therapies that harness the immune system to fight cancer. With the launch of this combination trial, the Company is taking a major step towards realizing the full potential of its Decoy platform. Indaptus Therapeutics has evolved from more than a century of immunotherapy advances. The Company’s novel approach is based on the hypothesis that efficient activation of both innate and adaptive immune cells and pathways and associated anti-tumor and anti-viral immune responses will require a multi-targeted package of immune system-activating signals that can be administered safely intravenously (i.v.). Indaptus’ patented technology is composed of single strains of attenuated and killed, non-pathogenic, Gram-negative bacteria producing a multiple Toll-like receptor (TLR), Nucleotide oligomerization domain (NOD)-like receptor (NLR) and Stimulator of interferon genes (STING) agonist Decoy platform. The product candidates are designed to have reduced i.v. toxicity, but largely uncompromised ability to prime or activate many of the cells and pathways of innate and adaptive immunity. Decoy product candidates represent an antigen-agnostic technology that have produced single-agent activity against metastatic pancreatic and orthotopic colorectal carcinomas, single agent eradication of established antigen-expressing breast carcinoma, as well as combination-mediated eradication of established hepatocellular carcinomas, pancreatic and non-Hodgkin’s lymphomas in standard pre-clinical models, including syngeneic mouse tumors and human tumor xenografts. In pre-clinical studies tumor eradication was observed with Decoy product candidates in combination with anti-PD-1 checkpoint therapy, low-dose chemotherapy, a non-steroidal anti-inflammatory drug, or an approved, targeted antibody. Combination-based tumor eradication in pre-clinical models produced innate and adaptive immunological memory, involved activation of both innate and adaptive immune cells, and was associated with induction of innate and adaptive immune pathways in tumors after only one i.v. dose of Decoy product, with associated “cold” to “hot” tumor inflammation signature transition. IND-enabling, nonclinical toxicology studies demonstrated i.v. administration without sustained induction of hallmark biomarkers of cytokine release syndromes, possibly due to passive targeting to liver, spleen, and tumor, followed by rapid elimination of the product. Indaptus’ Decoy product candidates have also produced significant single agent activity against chronic hepatitis B virus (HBV) and chronic human immunodeficiency virus (HIV) infections in pre-clinical models. The content above comes from the network. if any infringement, please contact us to modify.

iStock, Noppharat05081977 The explosion of GLP-1 weight loss drugs is reminiscent of the early days of PD-1 inhibitors, but key market differences suggest history may not repeat itself. If you’ve been around drug development for a while, the rise of GLP-1 therapies might sound familiar to you: a breakthrough emerges after years of hard work in the clinic. A leader captures the market. Billions are made. Copycats follow, hoping for a slice of the pie. It’s the story of PD-1 inhibitors and the immunotherapy boom that redefined how we treat cancer a decade ago. Many industry insiders often call back to this cancer revolution when talking about the meteoric rise of GLP-1s. But within the storied history of PD-1s lies a flashing warning sign for the “fast-follower” approach, experts say. That’s because the harsh reality that was laid bare with PD-1 inhibitors is that many of the companies gambling on being the second or third drug in an indication will not be successful. Despite oncology being the dominant market for R&D over the last decade, “there are a large number of biotech companies, as well as Big Pharma companies, rushing to enter the GLP-1 space at a rate not seen before, even with PD-1s,” Akash Patel, a pharma analyst at GlobalData, told BioSpace . “The race out of the gate to achieve a highly efficacious GLP-1 therapy has been huge.” Winners and Losers in the PD-1 Space Keytruda was the first approved PD-1 therapy, entering the market in September 2014, but the jockeying for supremacy in the space began well before that drug was ever approved. Merck’s immuno-oncology juggernaut was not always the dominant cancer therapeutic. While Bristol Myers Squibb’s PD-1 therapy Opdivo was approved second in December 2014, it quickly established a sales lead. By the end of 2015, Opdivo had generated $942 million in full year sales against Keytruda’s $566 million. “Initially, Bristol Myers Squibb was dominating that race—they had broader approvals and bigger indications,” Matt Phipps, a partner at William Blair, told BioSpace . “And then Merck completely took over based on better trial design and approvals in lung cancer.” Fast forward to 2024, full-year results show the gulf that now exists between the two treatments, with Keytruda generating global sales of $29.4 billion—by far the best-selling drug of the year —while Opdivo brought in just $9.3 billion worldwide. That was, however, still enough to make the number nine slot on the list of the top-10 best selling drugs of 2024 , and is still a healthy earner for BMS. Opdivo’s sales fell away from Keytruda around 2018 and have never made up the gap; sales produced by both treatments show the scale of the market and the opportunity for competitors to carve out a smaller, but substantial, slice. There are other examples of drugs that were developed later but ultimately became more successful, Phipps noted, such as with statins and TNF-alpha inhibitors. This history suggests that subsequent weight loss drug developers could catch up to Eli Lilly and Novo Nordisk, the current market leaders . Beyond the big two PD-1 therapies, there was still space for two other major entrants to carve out a market share, in Roche’s Tecentriq and AstraZeneca’s Imfinzi, both of which inhibit PD-1’s molecular partner, PD-L1, Phipps said. Of the treatments that arrived later to market, the strategy has been to go after smaller indications that were not already targeted by BMS or Merck. Roche’s PD-1 Tecentriq, for example, achieved sales of $4.1 billion worldwide in 2024, becoming the Swiss pharma’s leading oncology seller. AstraZeneca’s PD-1 Imfinzi brought in $4.7 billion the same year, the third-largest drug overall for the U.K. company. Even against such heavyweights, smaller companies are still pushing forward with PD-1s. Incyte Biosciences received approval for its PD-1 inhibitor, Zynyz, in 2023 . The drug brought in sales of $3 million for the full year 2024. When asked about the possibility to differentiate in a competitive space, an Incyte spokesperson told BioSpace the company sees an opportunity to “meet the needs of different patient populations.” Incyte is aiming to make Zynyz the first PD-1–targeting drug to achieve approval against squamous cell anal carcinoma with the POD1UM-303/InterAACT2 trial currently in Phase III. But those are just the successful examples. The clinical record is also littered with failed followers. The PD-1 market witnessed a surge of R&D, but both Big Pharmas and small-scale biotechs struggled to translate this into successful treatments. Pfizer developed Bavencio with Merck KGaA,which was fourth-to-market but struggled to achieve significant sales, leading Pfizer to return the drug’s rights to its partner in 2023. The treatment is still marketed by Merck KGaA but managed only $735 million in full-year 2024 results. The same occurred with Novartis’ PD-1 treatment Tevimbra, developed alongside BeiGene, with the partnership on the drug cancelled in 2023. The treatment is still on the market but had just $621 million in full-year 2024 sales. The relative failure of these treatments shows that even the financial firepower of Big Pharma is not always enough to successfully break into the market as a fast follower. For small-cap companies, Phipps said that many tried to develop combination therapies to improve efficacy over monotherapies and retain ownership of their assets. However, this approach “didn’t really pan out to be as good as they hoped,” due to the failures to show improved efficacy. This resulted in various unsuccessful partnerships, such as Nektar Therapeutics and BMS’ investigational combination therapy . A similar story unfolded with Innate Pharma and AstraZeneca’s Phase III trial of monalizumab. One certainty for those investing in weight loss drugs is that, like PD-1s, there will be failures. Phipps thinks the fallout could be even more severe given the major differences between the two markets. Different Markets, Different Challenges Demand for PD-1 therapies was based on their potential to dramatically improve the survival chances of those with cancer. This was largely driven by physician prescribers. The GLP-1 market, on the other hand, is consumer-led. GLP-1 weight loss treatments have broken out of the traditional medical field and become instilled into the public consciousness, and even pop culture. The lower perceived medical necessity also means there are ongoing discussions between drug developers and payers over discounts to pricing and rebates in weight loss, which will impact revenue for any would-be entrants onto the market. The dynamic in the oncology market is different for PD-1s, with drug developers competing on efficacy and expanding on approved indications rather than on pricing . Another major drawback that Phipps identified is “patient churn,” where within one year most patients will stop taking GLP-1 treatments, with these figures declining even further at the two-year mark. By comparison, PD-1 drugs were initially approved when there were no other treatment options, which meant patients would complete treatment courses because there were no alternative pathways for recovery from cancer. The urgency of treating cancer, for both patients and physicians, therefore does not allow for direct parallels to be drawn between sales growth for PD-1s and GLP-1s. This differing market dynamic led Phipps to caution that some estimates suggesting the weight loss drug market will continue to expand at current rates are likely flawed. Analysts have put potential sales as high as $150 billion by the early 2030s, but Phipps does not think the market will reach that because drug developers have not yet solved the problem of how to keep people on the therapies. Without patient retention, revenues for any potential treatment developed could be limited, with Phipps noting that both Novo Nordisk and Eli Lilly delivered 2025 guidance that was “a little below analysts’ expectations,” though he added that this could also be due to manufacturing issues. One area that could unfold similarly in the journeys of PD-1s and GLP-1s is the gathering of indications. Expanding a drug’s label can help extend its patent exclusivity period and boost revenue. Since Keytruda’s 2014 approval, Merck has gone to work collecting indications to add to its roster. The drug is now approved to treat nearly 50 different types and stages of cancer, from lung to melanoma, breast to non-Hodgkin lymphoma. The drug has also been granted biomarker-based approvals allowing its use with certain genetic mutations regardless of tumor type. Oncology offersa far broader range of potential indications for drug developers than those available to GLP-1 drug developers. But obesity companies could still follow this playbook, Patel said. Indeed, Novo and Lilly are pursuing a similar strategy for their weight loss drugs. Novo’s Wegovy has received a label expansion for reducing cardiovascular risk . Lilly, meanwhile, added an FDA nod for the treatment of obstructive sleep apnea . The companies are also pursuing metabolic dysfunction-associated steatohepatitis (MASH), kidney disease , Alzheimer’s and alcohol use disorder , among other indications. For investors seeking a potential blockbuster weight loss drug that could emerge from a heaping pile of options, Phipps said there are three important considerations: improving efficacy, improving tolerability and being a small molecule formulation. Each could potentially offer advantages over current treatments, with greater weight loss potentially attracting more patient interest, improved tolerability allowing people to take the treatment for longer and small molecules offering significant manufacturing and dosing advantages, such as the ability to be taken orally. This is different from the early stages of the PD-1 market, Phipps noted, where the focus was on quickly developing a “me-too” treatment. As a result, he said, investing in the obesity space is “less enticing” because of the complexity of developing a differentiated product. What is not yet clear is which approach investors will favor, with Phipps describing the market as being in the “early innings” of discovering how to best serve patients.