Tizona Therapeutics, Inc.

TTX-080 plus EGFR Inhibitor Cetuximab Demonstrated Promising Evidence of Clinical Activity in Patients with Biomarker-Defined Metastatic Colorectal Cancer and Locally Advanced/Metastatic Head and Neck Squamous Cell Carcinoma TTX-080 Exhibited Significant On-Mechanism Immune Cell Changes in the Periphery and in Tumors SOUTH SAN FRANCISCO, Calif., May 23, 2024 (GLOBE NEWSWIRE) -- Tizona Therapeutics, Inc., a privately held, clinical-stage company developing cancer immunotherapies, today announced first-in-human Phase 1b clinical data of TTX-080, a novel, first-in-class, antibody targeting HLA-G, in patients with metastatic colorectal cancer (mCRC) and locally advanced/metastatic head and neck squamous cell carcinoma (mHNSCC). The preliminary data will be presented during a poster session on June 1, 2024, at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago, IL. “Metastatic colorectal cancer is a global health issue, affecting men and women equally and with rising incidence among young adults. Despite treatment advances in the last 25 years, more therapeutic options are needed for those with good performance status, but whose disease has become unresponsive to available therapies. Additionally, the prognosis for patients with metastatic head and neck squamous cell carcinoma is generally poor, also requiring new treatment approaches to treat this disease,” said OU Health Stephenson Cancer Center hematologist/oncologist Susanna V. Ulahannan, M.D., MMEd, Associate Professor in the Section of Hematology/Oncology at OU College of Medicine at the University of Oklahoma Health Sciences and Presenting Author for the TTX-080 Phase 1 clinical trial. “The addition of TTX-080 to standard-of-care cetuximab showed promising clinical activity in subsets of biomarker-defined patients who have received multiple lines of prior therapies, including chemotherapy, antiangiogenic and immunotherapy agents. We look forward to additional studies that further explore the role of TTX-080 for these difficult-to-treat cancers in a high unmet need patient population.” Clinical Trial Results Results from Ph1a/1b Analyses of TTX-080, a First-in-Class HLA-G Antagonist, in Combination with Cetuximab in Patients with Metastatic Colorectal Cancer and Head and Neck Squamous Cell Carcinoma The Phase 1 open-label, dose escalation and dose expansion clinical trial of TTX-080 evaluated safety, tolerability, recommended Phase 2 dose and preliminary efficacy of TTX-080 as monotherapy and in combination with either cetuximab, an EGFR inhibitor, or pembrolizumab, a PD-1 inhibitor, in patients with advanced refractory/resistant solid tumors (n=240). The clinical results that will be presented at ASCO focus on the safety and efficacy from the Phase 1b cohorts of the trial, evaluating TTX-080 in combination with cetuximab in patients with anti-EGFR-naïve, wild-type (WT) KRAS mCRC (n=25) and mHNSCC cancers (n=23), with a data cutoff of April 15, 2024. Additional information about the clinical trial can be found on clinicaltrials.gov (NCT04485013). TTX-080 was well tolerated as monotherapy and in combination with cetuximab in patients with mCRC and mHNSCC. Metastatic Colorectal Cancer Results The most common Grade 3 adverse events (AEs) in patients with mCRC were increases in AST (n=3) and ALT (n=3), fatigue (n=1), dermatitis acneiform (n=1) and myalgias (n=1). TTX-080 plus cetuximab demonstrated anti-tumor activity in patients with WT RAS, BRAF, HER2-negative mCRC. Patients in this subgroup had received a median of 2 prior lines of treatment (Range 1,5). All patients had received 5-fluoropyrimidine. Seventy-eight percent (78%) of patients had received prior bevacizumab and more than 75% had received oxaliplatin and or irinotecan. Median progression-free survival (PFS) was 24.4 weeks, with a 36-week PFS rate of 47%. In 14 tumor response evaluable patients with WT RAS, BRAF, HER2-negative mCRC, TTX-080 plus cetuximab achieved an overall best response (ORR) in 4 patients (29%), a partial response (PR) in 4 patients (29%) and stable disease (SD) in 6 patients (43%). Nine (9) of 13 (69%) patients had at least 15% target lesion regression and 10 of 14 patients had disease control rate (DCR) of greater than 90 days (71%). Locally Advanced/Metastatic Head and Neck Squamous Cell Carcinoma Results The most common Grade 2 AEs were anemia (n=2), fatigue (n=1) and an increase in AST (n=1). One (1) patient experienced Grade 4 anemia. TTX-080 in combination with cetuximab generated anti-tumor activity in patients with human papillomavirus (HPV)-negative mHNSCC. Patients in this subgroup had received a median of 1 prior line of treatment (Range 1, 2). All patients had received a prior immunotherapy treatment. Median PFS was 23.9 weeks, with a 24-week PFS rate of 43%. In 7 tumor response evaluable patients, TTX-080 plus cetuximab achieved an overall best response (ORR) in 4 patients (57%), 1 CR (14%), 3 PRs (43%) and 1 SD (14%). Five (5) patients (71%) had at least 20% target lesion regression and DCR of greater than 90 days (71%). “These Phase 1b clinical results boost our confidence that TTX-080 in combination with cetuximab may improve clinical outcomes in patients with biomarker-defined advanced colorectal cancer and head and neck squamous cell carcinoma,” said Swami Murugappan, M.D., Ph.D., Consulting Chief Medical Officer at Tizona Therapeutics. “Our goal is to confirm these Phase 1b results in subsequent clinical trials.” Translational Results HLA-G, an MHC class I molecule expressed on solid tumors, is known to drive immune suppression, promote cancer cell immune escape and lead to tumor development and growth. HLA-G mediates suppression through ILT2 and ILT4 on lymphoid (ILT2) and myeloid (ILT2 & ILT4) cell subpopulations. TTX-080 is designed to block HLA-G to reverse immune tolerance and activate anti-tumor immune responses. TTX-080 induced statistically significant on-mechanism immune cell activation in the periphery and in the tumor. Peripheral changes were detected using flow cytometry in patient peripheral blood mononuclear cells (PBMCs). Increased percentages of activated Ki67+ natural killer (NK) cells, - ILT2+ CD8+ T cells and of activated Ki67+PD-1+HLA-DR+ CD4+ T cells. Monotherapy TTX-080 also led to changes in the tumor, with the detection of increased myeloid activation gene sets known to be associated with anti-tumor activity. Poster Details Poster Session: Developmental Therapeutics – ImmunotherapyDate/Time: June 1, 2024, at 9:00 a.m. CDTAbstract: 2524 | Poster Board #3Location: Hall A About Tizona Therapeutics, Inc. Tizona is a privately held, clinical-stage immunotherapy company that develops first-in-class medicines to deliver transformational benefits for people with cancer. Tizona translates scientific breakthroughs into therapeutics that stimulate the immune system and counter immune suppression. Tizona’s pipeline includes TTX-080, which targets HLA-G and is being evaluated in a Phase 1b clinical study in advanced cancers. Media ContactLori Murraylori.murray@captivate-comms.com

Besides its HIV franchise, Gilead is counting on its cell therapies and its antibody-drug conjugate, Trodelvy, to help drive growth. Despite markedly slower cell therapy growth from the third to the fourth quarter of 2023—and a recent setback for Trodelvy—historically HIV-focused Gilead Sciences is not discouraged amid its oncology push. Most recently on Gilead's quest to become a major oncology player, the company scored an FDA nod for a new manufacturing process change for its CAR-T drug Yescarta, shortening the production timeline from seven to five days and allowing for a median turnaround time of 14 days. The improvement puts Gilead's cell therapy manufacturing ahead of its peers and is “just the beginning of what we can continue to do with this business,” Chief Financial Officer Andrew Dickinson said Tuesday on Gilead’s fourth-quarter and full-year conference call. Besides Gilead's advantage on turnaround timelines, industrywide supply challenges in viral vector manufacturing are “something we are not suffering from," Cindy Perettie, executive vice president of Gilead's cell therapy group Kite Pharma, added on the call. That's because the company runs its own viral vector manufacturing facility, she explained. A recent Kite Pharma restructuring, meanwhile, should “continue to drive growth and efficiency” over the long run, Dickinson said. The company recently cut 7% of its workforce but added 90 roles, netting out to around a 5% overall reduction, a Gilead spokesperson told Fierce Biotech. “We’re really growing the business for long-term sustainability and growth and less near-term profitability,” Dickenson said, adding that it's “certainly exciting” that the franchise is doing “as well as it is.” During the fourth quarter, cell therapies Yescarta and Tecartus increased sales (PDF) 11% to $466 million, a slower growth rate than the 22% jump seen during quarter three. Gilead previously noted that a major barrier in CAR-T uptake can be attributed to a mismatch between where the majority of oncology patients are treated and where the company’s authorized treatment centers (ATCs) operate, which is largely in major academic centers. The constraints within the ATC footprint marked a contributing factor to the fourth-quarter growth downturn, Perettie said. In response, Gilead aims to expand the footprint of treatment centers, which currently total 400, to “meet patients where they are.” While the effort is a key aspect to Gilead's cell therapy business strategy, it takes “a little bit longer,” meaning growth is likely to be flat to slightly up in the first quarter of 2024 and return during the second half of the year, Perettie noted.   Another major drug in Gilead’s oncology franchise is the antibody-drug conjugate (ADC) Trodelvy. That drug saw sales skyrocket by 56% over the full year and is a key driver for the company. Still, it took a blow last month with a failed study called EVOKE-01 in previously treated metastatic non-small cell lung cancer (NSCLC). Despite the missed endpoint, the company still looks to push forward in the front-line NSCLC setting with its EVOKE-03 trial. Gilead maintains a “very high” level of overall confidence in Trodelvy and its development program, Chief Medical Officer Merdad Parsey, M.D., Ph.D., said. Several phase 3 readouts are planned for this year, including a bladder cancer confirmatory study and an update to a triple-negative breast cancer trial. The full data set from the ill-fated EVOKE-01 study “maintains our level of enthusiasm” about the therapy’s long-term potential on the efficacy and safety side, Parsey added. Overall, Gilead aims to pull a third of its revenue from the oncology sector by 2030. In 2023, the number was around 11%. Outside of oncology, Gilead can typically lean on its stalwart HIV franchise. The company’s HIV meds took home the bulk of the bacon last year despite a 2% sales dip in the fourth quarter. In HIV, “you really need to focus on the full year” to track growth trends, Dickinson said. The franchise's yearly sales increase was 6%, reaching a total of $18.2 billion. Overall, Gilead’s full-year revenues totaled $27.1 billion, a 1% decline from the prior year. Excluding COVID antiviral Veklury, product sales grew 7%. Compared to its M&A hungry peers, Gilead has been notably less active in that department as of late. Just yesterday, the company confirmed in an email to Fierce Biotech that it was backing out of its Tizona Therapeutics buy option, an opportunity it paid $300 million for in 2020. Along with its confidence in in-house opportunities, the company will “continue to be opportunistic” about pursuing business development within its three focus areas of virology, oncology and inflammation, and it will look at “later-stage deals," CEO Daniel O’Day said on the call. For now, Gilead is content with its more than 20 study readouts planned for this year and a lack of upcoming patent expirations.  “We feel we have everything within Gilead right now to achieve our ambitions over the second half of this decade,” O’Day said on the call.

Gilead's agreement with Tizona centered on a novel checkpoint inhibitor targeting HLA-G. Gilead will not buy immunotherapy biotech Tizona Therapeutics, backing out of an option that the company paid $300 million for in 2020.  The pharma's opt-in oncology program with the biotech was absent from the company’s pipeline as of the end of 2023. Now, Gilead has confirmed in an email to Fierce Biotech that it will not opt into the deal. Gilead invested $300 million in Tizona back in July 2020 for nearly 50% of the company and exclusive rights to buy out the remainder for up to an additional $1.25 billion. At the center of the deal was TTX-080, a novel checkpoint inhibitor targeting HLA-G, that was on the precipice of a phase 1 trial at the time the deal was announced.  The trial has been ongoing for more than three years, testing TTX-080 as both a monotherapy and as a combo treatment with either Keytruda or Erbitux. An update to the clinical trial record posted a month ago deleted text in the description that said the study was enrolling in the dose expansion arms.  When announced, then-Tizona CEO Scott Clarke said that the deal would help fund further TTX-080 development but also advance “our rich, first-in-class preclinical portfolio and target validation efforts.” But no new programs are listed beyond TTX-080, and the “undisclosed programs” in the pipeline remain in the discovery stage.  As part of the Gilead deal, Tizona spun off its AbbVie-partnered antibody, TTX-030, into a separate entity.  Large equity deals have become a staple of Gilead’s business development efforts, with at least two announced in the last year. The Foster City pharma now owns a third of Arcus after a $320 million equity investment last month. And in October 2023, Gilead bought $15.2 million in equity of Assembly Bio, representing 19.9% of outstanding shares. Subject to certain conditions, GIlead agreed to buy up to 29.9% of outstanding shares at a premium. The deal with Assembly, which included $84.8 million upfront, gives Gilead first dibs to all of Assembly’s current and future programs throughout the 12-year deal.