On January 13, 2025 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company working to redefine the treatment of solid tumor cancers with cell therapy, reported that letetresgene autoleucel (lete-cel), has been granted breakthrough therapy designation by the U.S. FDA for the treatment of patients with unresectable or metastatic myxoid/round cell liposarcoma (MRCLS) who have received prior anthracycline-based chemotherapy, are positive for HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06, and whose tumor expresses the NY-ESO-1 antigen (Press release, Adaptimmune, JAN 13, 2025, View Source [SID1234649720]).

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More details about the Company’s sarcoma franchise, including the lete-cel clinical program and launch progress for TECELRA (afamitresgene autoleucel), the Company’s first commercial product and the first FDA approved engineered cell therapy for a solid tumor, will be provided during the Company’s presentation at the Annual J.P. Morgan Healthcare Conference, taking place in San Francisco, California, on Tuesday, January 14th, 2025, 4:30-5:10 PM PST (Webcast access here).

Breakthrough therapy designation for lete-cel in MRCLS was based on the results in this indication from the Phase II IGNYTE-ESO trial. The Company previously received breakthrough therapy designation for lete-cel for the treatment of synovial sarcoma in 2016. In the Phase II analysis, 27/64 (42%) people with synovial sarcoma or MRCLS had RECISTv1.1 responses by independent review, with 6 complete responses and 21 partial responses. The response rate was 14/34 (41%) for people with synovial sarcoma and 13/30 (43%) for people with MRCLS. The median duration of response (DoR) was 12.2 months (95% CI 6.8, 19.5). In synovial sarcoma, the median duration of response was 18.3 months (95% CI 3.3, -). In MRCLS, the median duration of response was 12.2 months (95%, CI 5.3, -). Safety findings were consistent with the known profile of lete-cel from previous data. All patients experienced treatment-emergent adverse events: cytopenias, cytokine release syndrome (CRS) and rash were the most common adverse events. Overall, toxicities were manageable, and consistent with an acceptable benefit to risk profile. Data from this trial were presented at the Connective Tissue Oncology Society (CTOS) 2024 annual meeting (Link to press release HERE; Presentation HERE).

Adrian Rawcliffe, Adaptimmune’s Chief Executive Office: "This designation by the FDA highlights the potential of lete-cel to address a critical need for new treatment options for patients with MRCLS. This is another important milestone in building out our sarcoma franchise, as we aim to bring lete-cel to market in 2026 for the treatment of synovial sarcoma and MRCLS. We look forward to initiating a rolling Biologics License Application for lete-cel later this year for the treatment of both sarcoma indications."

The breakthrough therapy designation is designed to expedite drug development and review processes. The criteria for this designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. With the designation, lete-cel will receive incentives, such as additional interaction and guidance from the FDA, the potential for a rolling submission, and potential priority review of the biologics license application, as well as other opportunities to expedite the development.

In addition to the Company’s presentation at J.P. Morgan, Adaptimmune will present the Company’s Allo-T program as a spin-out opportunity at the Biotech ShowCase and the Wuxi Global Forum 2025 Investor Roundtable. Details can be found below:

Biotech Showcase | Investor conference | Co-produced by Demy-Colton and EBD Group
Presentation at 2 p.m. PST on Tuesday, January 14th, Yosemite C, Hilton Hotel, Union Square.
WuXi Global Forum 2025 – WXPress: for WuXi news and R&D insights
Round Table Presentation at 5 p.m. PST on Tuesday, January 14th, Tower 3, Hilton Hotel, Union Square

On January 13, 2025 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab in previously untreated (first-line) cisplatin-ineligible patients with metastatic urothelial cancer (mUC) (Press release, Bicycle Therapeutics, JAN 13, 2025, View Source [SID1234649640]). The company also announced recent accomplishments and outlined strategic priorities and anticipated milestones for 2025.

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"Bicycle Therapeutics made significant advances across all aspects of our business in 2024. Notably, we drove important clinical progress of our targeted therapeutics in solid tumors, including greatly expanding the number of patients who could potentially benefit from our lead therapy zelenectide pevedotin, advanced our emerging pipeline of novel radiopharmaceuticals and strengthened our financial position and operational capabilities to advance our strategic priorities," said CEO Kevin Lee, Ph.D. "We are encouraged by our updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab in first-line cisplatin-ineligible patients, which we believe continue to demonstrate a differentiated safety profile and encouraging response rates in patients with poor prognosis and limited treatment options. We believe we are well-positioned to continue our strong momentum of execution over the course of 2025, which will be another year of important data milestones across our pipeline as we work to develop potentially transformative treatments that will help patients live longer and live well."

Updated Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data in First-Line mUC Highlights

Zelenectide pevedotin, a Bicycle Toxin Conjugate (BTC), has significant potential to treat Nectin-4 cancers. As of Jan. 3, 2025, updated topline results from the ongoing Phase 1 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2 weekly plus pembrolizumab 200 mg once every three weeks in 22 first-line cisplatin-ineligible patients with mUC showed:

· 65% overall response rate (ORR) (13/20) among all efficacy-evaluable patients, and a 50% ORR (10/20) among patients with confirmed responses. Of the 3 unconfirmed responses, 1 patient remained on treatment at the time of the data cut.
· Median duration of response (mDOR) is not yet mature, with 12 patients still on treatment at the time of the data cut.
· Safety and tolerability profile continues to be broadly consistent with other Phase 1 zelenectide pevedotin monotherapy and combination cohorts. Adverse events of clinical interest such as peripheral neuropathy, skin reactions and eye disorders were primarily low grade. All cases of Grade 3 treatment-related adverse events (TRAEs) of clinical interest were reversible, and there were no Grade 4 or Grade 5 TRAEs of clinical interest. Notably, no patients withdrew from the study due to zelenectide TRAEs.

Altogether, these updated data continue to position zelenectide pevedotin as a potentially promising best-in-class therapy for mUC.

Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 registrational trial evaluating zelenectide pevedotin plus pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and zelenectide pevedotin monotherapy and in combination with pembrolizumab in late-line mUC (Cohort 2). In each cohort, two doses of zelenectide pevedotin – 5 mg/m2 weekly and 6 mg/m2 two weeks on, one week off – are initially being assessed before a final dose is selected.

2024 Key Accomplishments

· Initiated the global Phase 2/3 Duravelo-2 trial for zelenectide pevedotin in mUC, providing multiple opportunities for potential accelerated approval.
· Presented updated monotherapy data for zelenectide pevedotin showing a promising 45% ORR in patients with late-line mUC who had not previously been treated with enfortumab vedotin. The data continue to support zelenectide pevedotin’s emerging differentiated profile as a potential treatment for mUC.
· Presented updated monotherapy data for BT5528, a BTC targeting EphA2, and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA), in advanced solid tumors. The data support each molecule’s emerging differentiated safety and tolerability profile and provide important information for continued dose selection exploration.
· Presented first human imaging data validating the potential of MT1-MMP as a novel target in the treatment of cancer and highlighting the potential of Bicycle molecules for targeted radionuclide therapy. The company also selected EphA2 as its second radiopharmaceutical target.
· Reported monotherapy data for zelenectide pevedotin showing an enhanced response in late-line breast cancer and non-small cell lung cancer (NSCLC) patients with NECTIN4 gene amplification and/or polysomy. Based on these data, the U.S. Food and Drug Administration granted Fast Track designation to zelenectide pevedotin for the treatment of adult patients with previously treated, NECTIN4-amplified, advanced or metastatic triple-negative breast cancer and NSCLC.
· Raised $555 million to help advance research and development and strategic priorities. As of Sept. 30, 2024, the company had $890.9 million in cash and cash equivalents, with expected financial runway into 2H 2027.

2025 Strategic Priorities and Anticipated Milestones

Seek to transform treatment across multiple Nectin-4 associated cancers with zelenectide pevedotin

· Report additional Phase 1 Duravelo-1 combination data with pembrolizumab in first-line cisplatin-ineligible mUC in 2H 2025.
· Report longer-term follow-up Phase 1 Duravelo-1 monotherapy data in late-line mUC in 2H 2025.
· Report Phase 2/3 Duravelo-2 Cohort 1 and Cohort 2 dose selection data in 2H 2025.
· Initiate Phase 1 trials in NECTIN4 gene-amplified breast cancer (Duravelo-3) in 1H 2025 and NECTIN4 gene-amplified lung cancer (Duravelo-4) and multi-tumor (Duravelo-5) in 2H 2025.

Advance emerging Bicycle Radionuclide Conjugates (BRC) pipeline and progress strategy for leadership in next-generation radiopharmaceuticals

· Report additional MT1-MMP human imaging data in mid-2025.
· Report initial EphA2 human imaging data in 2H 2025.

Advance targeted therapeutics pipeline addressing novel targets that have historically been challenging to treat

· Report Phase 1 combination data for BT5528 plus nivolumab in 4Q 2025.
· Report Phase 1 combination data for BT7480 plus nivolumab in 4Q 2025.

J.P. Morgan Healthcare Conference Presentation and Webcast

Bicycle Therapeutics will highlight these updates and strategic priorities in a corporate presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, Jan. 14, 2025, at 5:15 p.m. PT, followed by a question-and-answer breakout session at 5:35 p.m. PT.

A live webcast of the presentation will be accessible from the Investor section of the company’s website at www.bicycletherapeutics.com. A replay of the webcast will be archived and available following the event.

On January 13, 2025 Genprex presented its corporate presentation (Press release, Genprex, JAN 13, 2025, View Source [SID1234649656]).

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On January 13, 2025 Rakovina Therapeutics Inc. (TSX-V: RKV), a biopharmaceutical company dedicated to advancing new cancer therapies based on novel DNA-damage response technologies, reported the successful achievement of a shortlist of AI-generated molecules targeting ATR (Ataxia Telangiectasia and Rad3-related protein) with specific designs for central nervous system (CNS) penetration (Press release, Rakovina Therapeutics, JAN 13, 2025, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-announces-key-milestone-in-cancer-drug-innovation-in-collaboration-with-variational-ai [SID1234649672]).

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This milestone represents the first significant deliverable in Rakovina’s partnership with Variational AI, which leverages their state-of-the-art Enki platform to fast-track the discovery of innovative inhibitors for specific DNA damage response (DDR) kinase targets. ATR is an important drug target due its critical involvement in the DNA damage response (DDR). Its inhibition can lead to selective cancer cell death and improved therapeutic outcomes when combined with other treatments.

These new ATR-targeted inhibitors will now advance to chemical synthesis followed by preclinical validation, a critical step in Rakovina’s mission to address unmet medical needs in oncology.

Innovative Approach to Drug Discovery

The shortlisted molecules were developed using Variational AI’s proprietary Enki foundation model platform to generate novel chemical compounds from the estimated 1060 molecules in chemical space, far greater than any screening library. The platform identifies promising drug candidates while reducing timelines from years to just months. With CNS penetration capabilities, these molecules are poised to address cancers that metastasize to the brain or originate within the CNS, areas with historically limited treatment options.

This achievement is just the beginning of a dynamic journey. Rakovina is broadening its research scope with Variational AI to target additional DDR kinase pathways, with the vision of building a comprehensive pipeline of next-generation small-molecule therapies. By leveraging generative AI, the Company can eliminate traditional barriers, promising a new era of faster, more precise cancer treatment development.

"We are pleased to announce the achievement of this first milestone in our collaboration with Variational AI," said Jeffrey Bacha, Executive Chairman of Rakovina Therapeutics. "The identification of ATR-targeted drug candidates with CNS penetration exemplifies the transformative potential of AI in cancer therapy. This progress represents a meaningful step forward in our research and demonstrates the growing impact of AI in accelerating drug development and innovation in oncology."

On January 13, 2025 Scribe Therapeutics Inc., a genetic medicines company unlocking the potential of CRISPR to transform human health, reported the achievement of a success milestone for one of the targets in its research collaboration with Sanofi to develop in vivo CRISPR-based therapeutics (Press release, Scribe Therapeutics, JAN 13, 2025, View Source [SID1234649688]). Scribe is eligible to receive over $1.2 billion across all programs in milestone payments for the achievement of certain research, development, regulatory and commercial milestones, as well as high-single-digit to mid-teen royalties.

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"We are excited about the progress we have made towards creating potentially curative in vivo genetic medicines with a partner like Sanofi," said Benjamin Oakes, Ph.D., co-founder and Chief Executive Officer of Scribe. "The complementary expertise of our teams has enabled the program to move quickly and attain early validation of our CRISPR genome editing technologies. We look forward to further advancement of this program with a direct line of sight towards bringing breakthrough CRISPR-based therapeutics to patients with significant unmet need."

CRISPR by Design is Scribe’s data-driven design and engineering approach for optimizing its CRISPR-based platforms and assets, including X-Editing (XE) technologies, to drive forward a new era of transformative genetic medicines.

"Advancing our in vivo program with Sanofi speaks to the versatility and strength of Scribe’s CRISPR-based platforms," said Svetlana Lucas, Ph.D., Chief Business Officer at Scribe. "We are pleased to reach this important milestone and continue progressing our collaboration to accelerate and expand our patient impact globally."

Scribe announced its initial research collaboration with Sanofi for CRISPR-based cell therapies to address oncology indications in 2022, followed by an expansion in 2023 to advance in vivo medicines for genomic diseases.