On November 7, 2024 XOMA Royalty Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its third quarter 2024 financial results and highlighted recent activities (Press release, Xoma, NOV 7, 2024, View Source [SID1234647954]).

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"We continue to take a balanced approach to building a portfolio of sustainable cashflow streams by selectively acquiring royalty economics across the lifecycle of drug development," stated Owen Hughes, Chief Executive Officer of XOMA Royalty. "The September approval of MIPLYFFA, the first therapy approved for patients living with Niemann-Pick disease Type C, adds to our growing commercial royalty portfolio, while the recent transaction with Twist Bioscience further expands our early-stage portfolio, a key focus for us as we look to distribute risk across a diversified portfolio."

Key Third Quarter Events

Partner Event
Zevra Therapeutics The U.S. Food and Drug Administration (FDA) approved Zevra’s MIPLYFFA (arimoclomol) capsules as an orally delivered treatment for Niemann-Pick disease type C (NPC). MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of NPC in adult and pediatric patients 2 years of age and older.
Rezolute
Announced the sunRIZE Phase 3 clinical trial investigating ersodetug (RZ358) in patients with congenital hyperinsulinism (CHI) will begin enrolling patients in the U.S. in early 20251.

Received FDA clearance to initiate Phase 3 registrational study for ersodetug for the treatment of hypoglycemia due to tumor hyperinsulinism2.

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Johnson & Johnson Presented neoadjuvant TAR-200 plus cetrelimab Phase 2 data in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse neoadjuvant platinum-based chemotherapy and are scheduled for radical cystectomy at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress3.
Subsequent Events

Partner Event
Twist Bioscience XOMA Royalty completed a $15 million royalty monetization agreement with Twist, acquiring 50% of the future milestones and royalties and adding 60-plus partnered early-stage programs across 30 companies enabled by Twist Bioscience’s Biopharma Solutions business unit to the XOMA Royalty portfolio.
Johnson & Johnson Announced one of two Phase 3 clinical trials in difficult to treat muscle-invasive bladder cancer (MIBC) that included treatment with cetrelimab was being discontinued for not showing superiority to chemoradiation during a scheduled interim analysis4. Cetrelimab continues to be investigated in multiple other clinical trials.
Anticipated 2024 Events of Note

Partner Event
Takeda On December 12, 2024, Takeda will be hosting an R&D Day: Focus on Late-State Pipeline and Market Opportunity and has commented publicly mezagitamab will be discussed during this investor event.
Third Quarter 2024 Financial Results

XOMA Royalty recorded total income and revenues of $7.2 million for the third quarter of 2024, which included $6.5 million in estimated income associated with two commercial products in our portfolio. In the third quarter of 2023, XOMA Royalty reported total income and revenue of $0.8 million.

Research and development (R&D) expenses were $0.8 million in the third quarter of 2024, reflecting transitory clinical trial costs related to KIN-3248, an asset acquired in the Kinnate acquisition, which the Company currently is winding down. R&D expenses in the third quarter of 2023 were $25,000.

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General and administrative ("G&A") expenses were $8.0 million for the third quarter of 2024 compared with $6.4 million in the third quarter of 2023. The increase of $1.6 million was primarily comprised of $1.4 million in total costs incurred after our acquisition of Kinnate, which included $1.1 million in legal and consulting costs, $0.1 million in information technology costs, and $0.1 million in insurance costs. The remainder of the increased G&A expense reflects an increase of $0.2 million for salaries and related costs.

In the third quarter of 2024, as a result of communications with Agenus, XOMA Royalty evaluated the status of the partnered programs underlying the Agenus Royalty Purchase Agreement for potential impairment and recorded a one-time, non-cash impairment charge of $14.0 million and a reduction of royalty receivables of $14.0 million associated with Agenus.

In the third quarters of 2024 and 2023, G&A expenses included $2.6 million and $2.7 million, respectively, in non-cash stock-based compensation expenses.

Total interest expense in the third quarter of 2024 was $3.5 million, representing interest and costs related to the Blue Owl Loan established in December 2023.

The Company reported total other income, net, of $1.9 million in the third quarter of 2024, as compared to total other income, net, of $0.3 million in the corresponding period of 2023. The $1.6 million increase reflects a $1.3 million increase in investment income due to higher balances on our investments and the change in the market price for XOMA Royalty’s shares of Rezolute common stock.

Net loss for the third quarter of 2024 was $17.2 million, compared to a net loss of $5.5 million for the third quarter of 2023, primarily resulting from the $14.0 million non-cash impairment related to the Agenus Royalty Purchase Agreement.

On September 30, 2024, XOMA Royalty had cash and cash equivalents of $146.8 million (including $4.8 million in restricted cash). On December 31, 2023, XOMA Royalty had cash and cash equivalents of $159.6 million (including $6.3 million in restricted cash). During the third quarter of 2024, XOMA Royalty received $9.9 million in cash from royalty and commercial payments. Net cash used in operating activities during the quarter was $8.6 million. On October 15, 2024, the Company paid a total of $1.4 million in cash dividends on the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) and the 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO).

On November 7, 2024 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and announced financial results for the third quarter ended September 30, 2024 (Press release, Xilio Therapeutics, NOV 7, 2024, View Source [SID1234647953]).

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"Throughout the third quarter, our team continued to drive execution across all stages of our pipeline, including advancing our clinical development programs for vilastobart, a tumor-activated, Fc-enhanced anti-CTLA-4, and XTX301, a tumor-activated IL-12, toward key data milestones and potential value inflection points," said René Russo, Pharm.D., president and chief executive officer of Xilio. "We look forward to sharing initial data from our Phase 1C dose escalation trial of vilastobart in combination with atezolizumab as part of a late-breaker poster presentation at the SITC (Free SITC Whitepaper) Annual Meeting. In addition, we continue to advance multiple promising research-stage programs, including XTX501, our tumor-activated PD-1/IL-2, and tumor-activated immune cell engagers."

Pipeline and Business Updates

Vilastobart (XTX101): tumor-activated anti-CTLA-4

Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME).

● Xilio will present initial Phase 1C dose escalation data for vilastobart in combination with atezolizumab in a late-breaker poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting taking place in Houston, Texas, from November 6-10, 2024.
● In addition, Xilio continues to enroll patients in its ongoing Phase 2 clinical trial evaluating vilastobart in combination with atezolizumab in patients with metastatic MSS CRC, including patients with and without liver metastases.
● Xilio expects to report initial Phase 2 data for vilastobart in combination with atezolizumab in approximately 20 patients with MSS CRC in the fourth quarter of 2024 and in a total of approximately 40 patients with MSS CRC in the first quarter of 2025.

XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state.

● Xilio continues to enroll patients in Phase 1A monotherapy dose escalation and Phase 1B monotherapy dose expansion of its ongoing Phase 1 clinical trial of XTX301 in patients with advanced solid tumors.
● Xilio plans to report safety, pharmacokinetic and pharmacodynamic data from the ongoing Phase 1 clinical trial for XTX301 in the fourth quarter of 2024.

Tumor-Activated Bispecific and Immune Cell Engager Programs

Xilio is leveraging its proprietary platform to advance a pipeline of research-stage programs for tumor-activated bispecific and immune cell engager molecules, including tumor-activated immune cell engagers and tumor-activated effector-enhanced immune cell engagers.

● XTX501 is a tumor-activated bispecific PD-1/IL-2 designed to selectively stimulate PD-1 positive antigen-experienced T cells and enhance their function. XTX501 incorporates masking designed to overcome IL-2 receptor-mediated clearance and peripheral activity. Xilio is currently advancing initial investigational new drug (IND)-enabling activities for XTX501.
● Xilio will present preclinical data from its tumor-activated SELECTIVE EFFECTOR-ENHANCED CELL ENGAGER (SEECR) format in a poster session at the SITC (Free SITC Whitepaper) Annual Meeting. Details on the poster presentation can be found here.

Third Quarter 2024 Financial Results

● Cash Position: Cash and cash equivalents were $61.3 million as of September 30, 2024, compared to $44.7 million as of December 31, 2023.
● License Revenue: License revenue was $2.3 million for the quarter ended September 30, 2024, which consisted of revenue recognized under the license agreement and stock purchase agreement with Gilead. No license revenue was recognized for the quarter ended September 30, 2023.
● Research & Development (R&D) Expenses: R&D expenses were $10.8 million for the quarter ended September 30, 2024, compared to $11.1 million for the quarter ended September 30, 2023. The decrease was primarily driven by decreased clinical development activities for XTX202, a tumor-activated, IL-2, decreased spending related to early-stage programs and indirect research and development costs and decreased personnel-related costs, partially offset by increased clinical development activities for vilastobart and XTX301.
● General & Administrative (G&A) Expenses: G&A expenses were $6.3 million for
for each of the quarters ended September 30, 2024 and September 30, 2023.

● Net Loss: Net loss was $14.0 million for the quarter ended September 30, 2024, compared to $16.7 million for the quarter ended September 30, 2023.
Financial Guidance

Based on its current operating plans, Xilio anticipates that its existing cash and cash equivalents as of September 30, 2024, will be sufficient to fund its operating expenses and capital expenditure requirements through the end of the second quarter of 2025.

About Vilastobart (XTX101) and the Phase 1/2 Combination Clinical Trial

Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). In 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab (Tecentriq) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety of the combination in Phase 1C dose escalation in patients with advanced solid tumors and the safety and efficacy of the combination in Phase 2 in patients with metastatic microsatellite stable colorectal cancer with and without liver metastases. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

About XTX301 and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio’s tumor-activated IL-12 program, including XTX301. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

On November 7, 2024 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat oncology indications, reported it has extended its previously announced Research Funding and Option Agreement (the "Agreement") with The Scripps Research Institute ("TSRI") to advance the development of the Company’s program on the combination of systemic DNase and CAR T-cell therapies (Press release, Xenetic Biosciences, NOV 7, 2024, https://ir.xeneticbio.com/news/detail/153/xenetic-biosciences-inc-extends-research-and-development-collaboration-with-the-scripps-research-institute-to-advance-dnase-platform [SID1234647952]). Xenetic’s systemic DNase I candidate is undergoing preclinical evaluation in combination with anti-CD19 CAR-T and anti-EGFR CAR-T cells in models of CD19-expressing hematological cancers and EGFR-expressing metastatic melanoma. Previous studies at TSRI showed that co-administration of DNase I with CAR T cells significantly reduces tumor burden, decreases the number of metastatic foci, and substantially prolongs survival compared to the CAR-T cell monotherapy groups. Degrading of NETs by DNase I increases the amount of tumor-infiltrating T and CAR-T cells and reduces the immunosuppressive effects of the tumor microenvironment (TME).

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Collected preclinical data highlights the critical role of NETs in modulating CAR-T cell efficacy and we believe provides a compelling rationale for incorporating DNase I as an adjunctive treatment to improve therapeutic responses in patients undergoing CAR-T cell therapy.

Xenetic’s DNase-based oncology platform is designed to target neutrophil extracellular traps (NETs), which are weblike structures composed of extracellular chromatin coated with histones and other proteins. In cancer, NETs are expelled by activated neutrophils into the TME and blood, thereby promoting cancer spread and local and systemic immunosuppression. Reduction of NETs burden via application of Xenetic’s proprietary recombinant human DNase I has been shown to improve efficacy of immunotherapy, adoptive cell therapy and chemotherapy in preclinical animal models.

"Scripps has continued to be a valued partner of ours and we are pleased to extend our collaboration agreement to further explore the potential of our DNase-based oncology platform. We are grateful we are able to continue to leverage the knowledge and expertise of the team at Scripps to potentially expand and broaden the utility of our proprietary platform technology," commented James Parslow, Interim Chief Executive Officer and Chief Financial Officer of Xenetic.

Under the terms of the Scripps Research agreement, in addition to advancing Xenetic’s existing intellectual property, Xenetic has an option to acquire an exclusive license to any new intellectual property arising from the DNase research program. Xenetic is executing on its plans to advance its DNase-based oncology program towards Phase 1 clinical development for the treatment of pancreatic carcinoma and other locally advanced or metastatic solid tumors.

On November 7, 2024 Werewolf Therapeutics, Inc. (the "Company" or "Werewolf") (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions, reported a business update and announced financial results for the third quarter ended September 30, 2024 (Press release, Werewolf Therapeutics, NOV 7, 2024, View Source [SID1234647951]).

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"Werewolf continues to progress our pipeline of INDUKINE therapeutics, led by WTX-124 and WTX-330, which have together provided preliminary clinical validation of our innovative design. To date, initial datasets from both programs have highlighted well-tolerated monotherapy activity in the outpatient setting, establishing WTX-124’s potential best-in-class profile among next-generation approaches to IL-2 and WTX-330’s potential first-in-class design which enables a wider exposure and therapeutic window of IL-12 than previously achieved," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We continue to progress WTX-124, with both monotherapy and combination expansion arms enrolling in multiple indications. We anticipate sharing monotherapy expansion data in the first half of 2025, which we expect will guide the next steps for the development program. In addition, we look forward to presenting interim data from our Phase 1 WTX-330 clinical trial at SITC (Free SITC Whitepaper) this weekend, including the emerging tolerability and clinical activity profile for WTX-330."

Recent Highlights and Upcoming Milestones

WTX-124: a systemically delivered, conditionally activated Interleukin-2 (IL-2) INDUKINE molecule being developed as monotherapy and in combination with pembrolizumab in multiple solid tumor types.
•Werewolf continues to progress the ongoing Phase 1/1b clinical trial evaluating WTX-124 as a monotherapy and in combination with pembrolizumab.
◦Following the selection of 18 mg WTX-124 administered intravenously every two weeks (IV Q2W) as the monotherapy recommended dose for expansion (RDE), the Company has opened monotherapy expansion arms and is actively enrolling patients with metastatic melanoma, renal cell carcinoma (RCC) and cutaneous squamous cell carcinoma (CSCC) who have failed immune checkpoint inhibitor therapy.
◦The Company has also selected 18 mg WTX-124 administered IV Q2W as its RDE for the combination with pembrolizumab and has opened combination expansion arms in metastatic melanoma, RCC, and non-small cell lung cancer (NSCLC).
◦Previously, the Company disclosed that two patients with metastatic melanoma treated in the 12 mg combination dose escalation cohort had partial and near-partial responses observed in preliminary data. Both patients now have confirmed partial responses, and both patients have remained progression free on study for more than 7 months.
◦The Company also previously disclosed that one patient with advanced CSCC treated in the 12 mg monotherapy dose escalation cohort had a documented complete response and then discontinued study drug at 21 weeks. This patient has remained in complete remission for over twelve months.
◦Cumulative biomarker data from tumor biopsies continue to provide evidence that baseline CD8+ effector T cells are relevant to clinical responses and that there is no evidence of Treg activation with treatment.

•In the first half of 2025, Werewolf expects to provide an update on the WTX-124 clinical development program, including data from the monotherapy expansion arms that are evaluating WTX-124 in more homogenous, less heavily pre-treated patient populations to inform future development priorities.
•Pending additional insight into the clinical profile, Werewolf intends to engage with regulators to discuss potential registrational pathways for WTX-124, including strategies for monotherapy accelerated approval.
WTX-330: a systemically delivered, conditionally activated Interleukin-12 (IL-12) INDUKINE molecule being developed in advanced or metastatic solid tumors.
•Werewolf plans to present updated interim safety and efficacy data from its ongoing Phase 1 clinical trial of WTX-330 in patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held November 6-10, 2024, in Houston, Texas. Presentation details are as follows:
◦Title: The tumor-activated IL-12 prodrug WTX-330 expanded/activated tumor infiltrating lymphocytes and caused tumor regression in patients with refractory solid tumors: Interim data from an ongoing Ph1 study
◦Abstract Number: 672
◦Session Date and Time: Saturday, Nov. 9, 2024; 9:00 a.m.–8:30 p.m. CT.
◦Location: George R. Brown Convention Center – Exhibit Halls A B
•In June 2024, the Company shared a preliminary program update, reflecting the same June 12, 2024, data cut-off as captured in the SITC (Free SITC Whitepaper) abstract, showing an improved therapeutic index with systemic administration of WTX-330, producing clinical activity at generally well-tolerated doses, with a 22-fold higher systemic prodrug exposure compared to recombinant IL-12 at its maximum tolerated dose.
•The data to be presented at SITC (Free SITC Whitepaper) will expand on this initial update, further characterizing safety, pharmacokinetics (PK), biomarkers and clinical activity and capturing additional patients treated since this data cut-off.
Preclinical Portfolio: includes development candidates WTX-712 and WTX-518, INDUKINE molecules targeting IL-21 and IL-18, respectively, for treatment of cancer and WTX-921, an INDUKINE molecule delivering IL-10 for treatment of inflammatory diseases.
•In October 2024, Werewolf announced the addition of WTX-921, a novel IL-10 INDUKINE development candidate for the treatment of inflammatory bowel disease and potentially other inflammatory diseases, to its pipeline, thereby increasing the breadth of the PREDATOR platform approach in therapeutic areas outside of oncology.
•At SITC (Free SITC Whitepaper), the Company plans to present a poster highlighting the distinct mechanisms by which IL-2, IL-12, binding protein resistant IL-18, and IL-21 accomplish antitumor immunity in mice. Presentation details are as follows:
◦Title: INDUKINE Molecules Delivering Various Cytokines Utilize Unique Mechanisms of Action to Drive Anti-Tumor Efficacy in Murine Syngeneic Tumor Models
◦Abstract Number: 955
◦Session Date and Time: Friday, Nov. 8, 2024; 9:00 a.m. – 8:30 p.m. CT.
◦Location: George R. Brown Convention Center – Exhibit Halls A B
Financial Results for the Third Quarter of 2024:
•Cash position: As of September 30, 2024, cash and cash equivalents were $122.8 million, compared to $135.3 million as of June 30, 2024. The Company believes its existing cash and cash equivalents as of September 30, 2024, will be sufficient to fund operational expenses and capital expenditure requirements through at least the second quarter of 2026.
•Collaboration revenue: No collaboration revenue was recognized during the third quarter of 2024 due to the fact that Werewolf substantially completed its performance obligations under the collaboration agreement with Jazz Pharmaceuticals (Jazz) during the second quarter of 2024. Comparatively, collaboration revenue was $5.9 million for the third quarter of 2023, which includes fixed payments received from Jazz, plus costs incurred for research services to be reimbursed by Jazz.
•Research and development expenses: Research and development expenses were $12.5 million for the third quarter of 2024, compared to $10.8 million for the same period in 2023. The increase in research and development expenses was primarily due to the Company’s development efforts for WTX-124 and WTX-330, which continue to progress through their respective clinical trials, resulting in higher clinical trial costs and higher manufacturing costs to support those trials.
•General and administrative expenses: General and administrative expenses were $4.6 million for the third quarter of 2024, compared to $4.3 million for the same period in 2023.
•Net loss: Net loss was $16.7 million for the third quarter of 2024, compared to $8.3 million for the same period in 2023.

On November 7, 2024 Tyra Biosciences, Inc. (Nasdaq: TYRA), a clinical-stage biotechnology company focused on developing next-generation precision medicines that target large opportunities in Fibroblast Growth Factor Receptor (FGFR) biology, reported financial results for the quarter ended September 30, 2024, and highlighted recent corporate progress (Press release, Tyra Biosciences, NOV 7, 2024, View Source [SID1234647950]).

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"These are exciting times at TYRA. We are very pleased with the interim data reported with TYRA-300 at ENA 2024. TYRA-300 demonstrated impressive anti-tumor activity at dose levels ≥ 90 mg once daily and was generally well-tolerated with infrequent FGFR1 and FGFR2 toxicities that limit the tolerability of pan-FGFR inhibitors. These data provide clinical support that an FGFR3 inhibitor designed to be highly selective can deliver meaningful clinical benefit to heavily pretreated patients with cancer," said Todd Harris, CEO of TYRA. "These results allow us to expand into larger studies for multiple bladder cancer indications, including metastatic urothelial cancer (mUC) and non-muscle invasive bladder cancer (NMIBC), while aiming to achieve best-in-class annualized growth velocity in achondroplasia (ACH). We look forward to initiating the Phase 2 study for ACH in the first quarter of 2025 and submitting an IND for NMIBC by the end of this year."

Third Quarter 2024 and Recent Corporate Highlights

TYRA-300

•
Reported Interim Clinical Proof-of-Concept Results from SURF301 Phase 1/2 Study (NCT05544552) in Patients with mUC. In October 2024, TYRA reported interim data with TYRA-300 during a late-breaking oral presentation at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain. The results included encouraging preliminary anti-tumor activity observed in a heavily pre-treated population: at ≥ 90 mg once daily (QD), 6 out of 11 (54.5%) patients with FGFR3+ mUC achieved a confirmed partial response (PR), with 100% disease control rate and sustained duration of activity; positive safety results were reported across all once-daily (QD) doses, with infrequent FGFR2/FGFR1-associated toxicities. The interim results warrant continued development of TYRA-300 for mUC and the Company is prioritizing QD dosing in SURF301 and future oncology studies. TYRA-300 is currently being evaluated in Part B of SURF301 at potentially therapeutic QD doses in preparation for potential future Phase 2 studies in NMIBC and mUC.

•
Phase 2 IND Submission for NMIBC on Track for Year-End 2024. TYRA plans to expand the clinical development of TYRA-300 into NMIBC to address the unmet needs in this cancer population with an efficacious, orally available therapy. TYRA remains on track to submit an Investigational New Drug (IND) application for a Phase 2 study of TYRA-300 in NMIBC before year-end 2024.
•
IND Clearance Received for Phase 2 Achondroplasia (ACH) Study (BEACH301). In October 2024, TYRA announced that the U.S. Food and Drug Administration (FDA) cleared its IND application for TYRA-300 allowing the company to proceed with a Phase 2 clinical trial of TYRA-300 for children with achondroplasia (BEACH301). The study will be a Phase 2, multicenter, open-label, dose-escalation/dose-expansion study evaluating TYRA-300 in children ages 3 to 10 with achondroplasia with open growth plates. The study will enroll children who are treatment-naïve (Cohort 1) and those who have received prior growth-accelerating therapy (Cohort 2) at multiple sites across the globe. Each of these cohorts is expected to enroll up to 10 participants per dose level (0.125, 0.25, 0.375, 0.50 mg/kg) for up to 12 months. Prior to initiation of Cohorts 1 and 2, the study will enroll a safety sentinel cohort of up to 3 treatment-naïve participants per dose level in children ages 5 to 10. TYRA expects to dose the first child with achondroplasia in BEACH301 in Q1 2025.
•
Peer-Reviewed Manuscript Published in Journal of Medicinal Chemistry. In September 2024, a manuscript titled "Discovery of TYRA-300: First oral selective FGFR3 inhibitor for the treatment of urothelial cancers and achondroplasia" was published in the Journal of Medicinal Chemistry (J. Chem) by the American Chemical Society. The published data provides preclinical evidence that TYRA-300 is a potentially best-in-class, novel precision small molecule designed to be selective for FGFR3 while sparing FGFR1 and 2 isoform toxicities and on-target gatekeeper resistant mutations. These results support the advancement of TYRA-300 in the ongoing SURF301 Phase 1/2 clinical study and the expansion into achondroplasia and hypochondroplasia.

TYRA-200

•
Phase 1 SURF201 Study Continued to Advance. The SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors) (NCT06160752) continued to advance. The study is a multi-center, open label study designed to evaluate the safety, tolerability, and PK of TYRA-200 and determine the optimal and maximum tolerated dose (MTD) and RP2D, as well as evaluate the preliminary antitumor activity of TYRA-200.

TYRA-200 is an investigational, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The SURF201 study is currently enrolling and dosing adults with unresectable locally advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating FGFR2 gene alterations.

TYRA-430

•
Continued Phase 1 Planning Following IND Clearance. TYRA announced that the FDA cleared its IND to proceed with a Phase 1 clinical study of TYRA-430, an investigational, FGFR4/3-biased inhibitor for FGF19+/FGFR4-driven cancers. The Phase 1 study will be a multicenter, open-label, first-in-human study of TYRA-430 in advanced hepatocellular carcinoma (HCC) and other solid tumors with activating FGF/FGFR pathway aberrations (SURF431). We believe TYRA-430 has the potential to address a significant unmet need in HCC, where there are no approved biomarker-driven, targeted therapies.

Corporate

•
Appointed Doug Warner, MD, as Chief Medical Officer (CMO). In September 2024, TYRA announced the appointment of Dr. Warner as CMO, who brings over twenty years of proven clinical development leadership to TYRA having successfully led global development and secured approvals for medicines across oncology and skeletal disease. Prior to TYRA, Dr. Warner held roles of increasing responsibility over 18 years at Amgen where he oversaw clinical development for programs across oncology and bone diseases. This included being an Executive Director and Group Product Area Lead, where Dr. Warner led a team responsible for the development of a portfolio of medicines ranging from those in Phase 1 to those with approved indications, including Vectibix, XGEVA, and Prolia. Most recently, Dr. Warner was Chief Medical Officer for eFFECTOR Therapeutics where he was responsible for overseeing eFFECTOR’s clinical pipeline, including its KICKSTART Phase 2b trial of tomivosertib in non-small cell lung cancer, and its Phase 1/2 study of zotatifin in solid tumors. Dr. Warner is co-author of numerous peer-reviewed articles including those in The Lancet, The Lancet Oncology, and The Journal of Clinical Oncology. He received his B.A. from the University of Pennsylvania, his M.D. from the Duke University School of Medicine, and his M.B.A. from the UCLA Anderson School of Management.

SNÅP Platform and Pipeline

•
TYRA continued to advance its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions.

Third Quarter 2024 Financial Results

•
Third quarter 2024 net loss was $24.0 million compared to $21.2 million for the same period in 2023.
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Third quarter 2024 research and development expenses were $22.7 million compared to $19.3 million for the same period in 2023. The increase was driven by increased expenses incurred in connection with our ongoing and planned clinical trials and personnel-related costs, partially offset by decreased drug manufacturing and preclinical costs.
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Third quarter 2024 general and administrative expenses were $5.9 million compared to $4.7 million for the same period in 2023. The increase was primarily driven by increased personnel-related costs, including stock-based compensation.
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As of September 30, 2024, TYRA had cash, cash equivalents, and marketable securities of $360.1 million. The Company’s current cash, cash equivalents and marketable securities are expected to allow TYRA to execute on its plans through at least 2026.

About TYRA-300

TYRA-300 is the Company’s lead precision medicine program stemming from its in-house SNÅP platform. TYRA-300 is an investigational, oral, FGFR3-selective inhibitor currently in development for the treatment of cancer and skeletal dysplasias, including achondroplasia and hypochondroplasia. In oncology, TYRA-300 is being evaluated in a multi-center, open label Phase 1/2 clinical study, SURF301 (Study in Untreated and Resistant FGFR3+ Advanced Solid Tumors) (NCT05544552). The study is designed to determine the optimal and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. Part A of the study included patients with all solid tumors who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg -120mg once-daily (QD). Part A of SURF301 is complete. The Company continues to advance TYRA-300 through dose expansion in Part B, which includes patients with solid tumors who are FGFR3+, to evaluate potentially therapeutic doses in preparation for potential future Phase 2 studies in metastatic urothelial carcinoma (mUC) and non-muscle invasive bladder cancer (NMIBC). In skeletal dysplasia, TYRA-300 has demonstrated positive preclinical results in achondroplasia and hypochondroplasia and TYRA has received IND clearance from the FDA to proceed with its BEACH301 clinical trial in children with achondroplasia.

About TYRA-200

TYRA-200 is an investigational, oral, FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations currently in development for the treatment of cancer. TYRA-200 is being evaluated in a multi-center, open label Phase 1 clinical study, SURF201 (Study in PrevioUsly treated and Resistant FGFR2+ Cholangiocarcinoma and Other Advanced Solid Tumors). SURF201 (NCT06160752) was designed to determine the optimal and MTD and the RP2D of TYRA-200, as well as to evaluate the preliminary antitumor activity of TYRA-200. SURF201 is currently enrolling adults with advanced/metastatic intrahepatic cholangiocarcinoma and other advanced solid tumors with activating alterations in FGFR2.