On February 15, 2024 Dragonfly Therapeutics, Inc., a clinical stage biotechnology company developing novel immunotherapies reported a new clinical collaboration designed to evaluate and combine DF1001, a HER-2 immune engager developed using Dragonfly’s TriNKET technology platform and Dragonfly’s lead clinical asset, with Trodelvy, Gilead’s Trop-2-directed antibody drug conjugate (ADC), in metastatic breast cancer (mBC) and non-small cell lung cancer (NSCLC) (Press release, Dragonfly Therapeutics, FEB 15, 2024, View Source [SID1234640165]).

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"DF1001 is the first of eight Dragonfly-developed drugs in the clinic and has shown clinical benefit in mBC, NSCLC and colorectal cancer (CRC) in a heterogeneous Phase 1 population with 22% RECIST responders and 39% clinical benefit in mBC patients at active dose levels, with no DLTs, even in a heavily-pre-treated population," said Joseph Eid, Dragonfly President of R&D. "It has been demonstrated to be well tolerated across all dose levels in the Phase 1 study as monotherapy, and pharmacodynamic activity was demonstrated in 28/42 (67%) paired biopsies from 0.5-15mg/kg, where increase in CD8 and NK cell infiltration was observed consistent with preclinical models and supporting the TriNKET immune modulating MoA. Our preclinical work has shown the powerful combinatorial effect of TriNKETs with ADCs, and highlighted the potential benefits to patients of using Gilead’s Trodelvy in combination with DF1001."

"We are delighted to further strengthen our partnership with Gilead by launching this new clinical stage collaboration," said Bill Haney, CEO and Dragonfly co-founder. "Dragonfly has promising pre-clinical data that highlights the potential for synergistic efficacy when DF1001 is combined with Trodelvy in mBC and NSCLC. We are excited to work with our colleagues at Gilead to bring this combination to patients in need."

Dragonfly will have operational control of the study and first patients are expected to receive this combination in Q2 2024. Clinical trial sites are currently open in the U.S., France, Belgium, Denmark and the Netherlands. Additional sites in North America, Europe and Asia Pacific will open in 2024. Additional information about the trial, including eligibility criteria, can be found at: View Source (ClinicalTrials.gov Identifier: NCT04143711).

About DF1001

DF1001 is an investigational first-in-class drug candidate that targets natural killer (NK) cells and T-cell activation signals to co-activating NK receptors, where NKG2D and CD16 co-stimulation yields distinctive and potent NK cell activation. DF1001 is being evaluated in adult patients for the treatment of advanced solid HER-2 positive tumors. DF1001 was discovered and developed using Dragonfly’s TriNKET platform. DF1001 has the potential to stimulate effective anti-tumor immunity in patients who are not eligible or not adequately responding to current therapies. DF1001 is the most advanced in a pipeline of TriNKETs that Dragonfly is developing to address high unmet needs for patients across a broad range of disease areas.

On February 15, 2024 Curadev reported CRD3874, a first-in-class allosteric small molecule STING agonist, with distinct pharmacological properties that distinguish it from agents that bind to STING’s cGAMP site (Press release, Curadev, FEB 15, 2024, View Source [SID1234640164]). An intravenous formulation of this lead asset (CRD3874-SI) recently received approval from the US FDA for use in first-in-human studies in patients with advanced solid cancers.

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Pre-clinical studies presented by Curadev at the annual meeting of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego, USA, in November 2023, showed that intravenous regimens of the drug caused robust immune-mediated tumor clearance in a range of tumor types in mice and that intravenous twice-weekly doses of CRD3874 as a single agent were well tolerated in monkeys. These features of CRD3874-SI predict a high therapeutic index in humans and support clinical investigation of this agent in cancer patients.

The poster was co-authored by Dr. Ciara Kelly, MD, Memorial Sloan Kettering Cancer Center, who is the PI for the FIH study (NCT06021626). Monali Banerjee, VP R&D at Curadev, who leads the STING programs and is the lead author of the poster, said, "CRD3874 is clearly unlike CDN-competitive STING agonists, since its distinct pharmacology and tolerability appear to be related to its allosteric binding mode. We are hopeful that the promising preclinical studies presented here will speak to the therapeutic potential of immune activation by CRD3874-SI in the context of advanced cancer in humans."

On February 15, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported that CEO, Bryan Kobel and Process Development Manager, Dr. Lauren Bor will be featured "Expert Speakers" at the 7th 7th CAR-TCR Summit Europe, February 27-29th in London, UK (Press release, TC Biopharm, FEB 15, 2024, View Source [SID1234640163]).

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Cell therapy industry experts will unite in for the only cell therapy conference looking in-depth at boosting clinical durability, advancing predictive biomarkers, and implementing safety switches through to automating production and accelerating analytical processes to reduce operational costs and turnaround times; and new cell therapy technology.

The 7th CAR-TCR Summit Europe provides exclusive access to the most cutting-edge advances across pre-clinical platforms, clinical advances, and streamlined manufacturing. The summit is your must-attend forum to stay at the forefront of cell therapy innovations. For more information or to register click here; View Source

On February 15, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), a leader in AI-driven cancer drug discovery and development, reported an important milestone in its antibody-drug conjugate (ADC) program (Press release, Lantern Pharma, FEB 15, 2024, View Source [SID1234640162]). In collaboration with Bielefeld University, Lantern has generated a new class of highly specific and highly potent ADCs with a cryptophycin drug-payload.

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This novel approach utilizes cysteine-engineered antibodies which allows for the development of uniform and homogenous ADCs with precise control of the drug to antibody ratio (DAR). The drug-payload, cryptophycin, has the potential to improve upon existing ADCs used in the clinical setting by: 1) improving the anti-tumor potency of the ADC molecule, and 2) overcoming drug resistance tumors can frequently develop to existing drug-payloads such as MMAE (Monomethyl auristatin E). The cryptophycin drug-payload and cryptophycin-ADC (CpADC) averaged an 80% cancer cell kill rate across the tested cancer cell lines and significantly outperformed MMAE.

In a broad range of preclinical studies, the cryptophycin-ADC (Cp-ADC) demonstrated promising picomolar level potency and anti-tumor activity in a wide range of solid tumors, including six cancer indications that are being further evaluated. These six indications include: breast, bladder, colorectal, gastric, pancreatic and ovarian cancer. Initial results (Figure 1) have also shown that in high Her2 expressing tumors, Cp-ADC with a DAR of 8 (Tras(C8)-Cp) and DAR of 4 (Tras(C4)-Cp) is more potent than an MMAE ADC with a DAR of 8. MMAE payloads are used in several commercially available anti-cancer ADCs, including Adcetris, Polivy and Enhertu. Additionally, the Cp-ADC with a lower DAR (Tras(C2)-Cp) provides an equivalent tumor kill-rate to that of an MMAE-ADC with a DAR of 8. In a moderate Her2 expressing cell line, the Cp-ADC with a DAR of 8 (Tras(C8)-Cp) was about 10 times more potent than a DAR 8 MMAE-ADC.

The newly developed Cp-ADC showed highly efficient anti-tumor activity in all six cancer cell lines with EC-50 values in the picomolar to single-digit nanomolar range. Additional studies are now being developed to further validate and expand these findings and to obtain a better understanding of the genomic and biomarker correlates of payload efficacy across these tumors.

Kishor Bhatia, Ph.D., Lantern’s Chief Scientific Officer commented, "Our strategic, data-driven approach of utilizing cryptophycin as a highly potent and novel payload alongside the prioritization of biologically novel and relevant targets with scalable and efficient drug conjugate formats will help expand the repertoire and diversity of ADC opportunities."

Lantern is also utilizing its AI platform, RADR to further refine and understand other cancer targets, with a focus on prioritizing targets that are expressed across multiple tumor types or subtypes and have few or no therapeutic ADC options. Given the promise of cryptophycin as a payload, Lantern is also focused on the development and testing of two other cryptophycin-ADC molecules. For these selected targets, Lantern is in advanced discussions with potential partners and collaborators with the goal of generating proof-of-concept data for these additional ADCs and potentially other novel drug conjugate formats. Lantern expects to provide additional details on these studies and collaborations in the coming quarters. These efforts aim to improve ADC development for specific patient populations and potentially guide more effective future clinical treatments with less cost and greater efficiency than historical ADC drug development.

On February 15, 2024 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") and Kelonia Therapeutics (CEO, Founder: Kevin Friedman, Ph.D., "Kelonia") reported that Xyphos Biosciences, Inc., (a wholly owned subsidiary of Astellas, "Xyphos") and Kelonia reported to have entered into a research collaboration and license agreement to develop novel Immuno-Oncology therapeutics (Press release, Astellas, FEB 15, 2024, View Source [SID1234640161]).

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Kelonia is a biotech company pioneering a new wave of genetic medicines using its in vivo gene placement system (iGPS). iGPS uses next generation lentiviral particles to efficiently deliver genetic cargo precisely to the desired target cells inside the patient’s body. Xyphos holds a novel and proprietary ACCEL technology*1 platform that uses its convertibleCAR (convertible Chimeric Antigen Receptor)*1 on immune cells.

Under the terms of the agreement, the companies plan to combine Kelonia’s iGPS with Xyphos’ ACCEL technology to develop innovative in vivo CAR-T Cell therapies*2 targeting up to two programs. Xyphos will be responsible for the development and commercialization of products created from the collaborative research. Kelonia will receive US $40 million upfront for the first program, and an additional US $35 million should Xyphos exercise its options for the second program, and potential milestones and contingency payments approaching US $800 million in total. Additionally, Kelonia will receive R&D funding for work performed in the collaboration and is eligible for tiered royalties on net sales up to the double digit percentage.

Kevin Friedman, Ph.D., CEO and Founder of Kelonia
"Our iGPS platform has the potential to be a step change in the treatment of cancer. Combining Kelonia’s in vivo gene delivery capabilities with the ACCEL convertible CAR technology is an ideal marriage of technologies to create off-the-shelf, universal CAR-T Cell therapies. We see revolutionary promise in this approach, and will work diligently with our partners at Astellas to unlock its full potential for patients that need it most."

Adam Pearson, Chief Strategy Officer (CStO) of Astellas
"At Astellas, we have a strong commitment to developing novel treatments for patients with cancer and have positioned Immuno-Oncology as a Primary Focus of our R&D strategy*3. With iGPS, Kelonia has an elegant, cutting-edge in vivo delivery technology, and by combining with the ACCEL platform, we believe the collaboration will bring synergies between the two companies’ breakthrough research and will ultimately lead to expansion of Astellas’ portfolio and to delivery of innovative in vivo CAR-T cell therapies to cancer patients."