On March 22, 2023 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 and year ended December 31, 2022, and highlighted recent corporate progress (Press release, Tyra Biosciences, MAR 22, 2023, View Source [SID1234629175]).

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"2022 was a momentous year for TYRA – we achieved significant milestones, evolved into a clinical-stage company, and leveraged our expertise in FGFR biology to expand our therapeutic focus beyond oncology to include genetically defined conditions," said Todd Harris, CEO of TYRA. "We believe TYRA-300 has the potential to become a best-in-class agent and we look forward to advancing it in both oncology and achondroplasia. Further, we have made steady progress utilizing our SNÅP discovery engine and expect to nominate additional clinical candidates."

Alan Fuhrman, CFO of TYRA, added, "TYRA is in a very strong financial position to begin 2023, with $251.2 million in cash and cash equivalents at year-end 2022, representing more than two years of expected cash runway to support our current development plans across our precision medicine platform."

Fourth Quarter 2022 and Recent Corporate Highlights

TYRA-300

Initiated SURF301 Phase 1/2 Study for Oncology. In November 2022, TYRA announced that patient dosing had commenced in its Phase 1/2 SURF301 clinical study of TYRA-300. SURF301 (NCT05544552) was designed to determine the optimal and maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300.
Expanded Development into Achondroplasia. In March 2023, TYRA announced the expansion of development of TYRA-300 into achondroplasia (ACH) based on positive preclinical results in a study performed in collaboration with the Imagine Institute in Paris, France. TYRA-300, an investigational agent, is a once-daily oral FGFR3 selective inhibitor whose design may have a meaningful impact on achondroplasia and other skeletal dysplasias.
In the study, TYRA-300 was evaluated in FGFR3 wild-type and mutant preclinical models to measure increases in growth and bone length, compared to vehicle-treated mice. In an FGFR3 Y367C/+ model, TYRA-300 was administered daily at a 1.2 mg/kg dose for 15 days. TYRA-300 increased body length in mice by 17.6% compared to the vehicle (p<0.0001) and increased the length of the femur (+24.4%), tibia (+38.3%) and L4-L6 (+23.9%) in mice (p<0.0001).
TYRA expects to submit an Investigational New Drug application (IND) to the U.S. Food and Drug Administration (FDA) to enable a Phase 2 study of TYRA-300 in pediatric achondroplasia in 2024.
TYRA-200

Announced IND Clearance. In March 2023, TYRA announced that the FDA cleared its IND to proceed with a Phase 1 clinical study of TYRA-200, an FGFR1/2/3 inhibitor with potency against activating FGFR2 gene alterations and resistance mutations. The trial will be focused on intrahepatic cholangiocarcinoma resistant to prior FGFR inhibitors. TYRA expects the first patient will be dosed in this trial in the second half of 2023.
SNÅP Platform and Pipeline

TYRA continued to use its in-house precision medicine discovery engine, SNÅP, to develop therapies in targeted oncology and genetically defined conditions including FGF19+/FGR4-driven cancers, and RET (REarranged during Transfection kinase) driven cancers.
Corporate

Strengthened Executive Team with Key Hire. During the fourth quarter of 2022, TYRA appointed experienced biotechnology veteran Alan Fuhrman as Chief Financial Officer.
Fourth Quarter and Full-Year 2022 Financial Results

Fourth quarter 2022 net loss was $12.9 million compared to $9.9 million for the same period in 2021.
Fourth quarter 2022 research and development expenses were $10.4 million compared to $7.2 million for the same period in 2021.
Fourth quarter 2022 general and administrative expenses were $4.6 million compared to $2.7 million for the same period in 2021.
Full year 2022 net loss was $55.3 million compared to $26.3 million for the same period in 2021.
Full year 2022 research and development expenses were $43.0 million compared to $20.6 million for the same period in 2021.
Full year 2022 general and administrative expenses were $15.9 million compared to $5.7 million for the same period in 2021.
As of December 31, 2022, TYRA had cash and cash equivalents of $251.2 million.
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. 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). SURF301 (NCT05544552) was designed to determine the optimal and maximum tolerated doses (MTD) and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to evaluate the preliminary antitumor activity of TYRA-300. SURF301 is currently enrolling adults with advanced urothelial carcinoma and other solid tumors with FGFR3 gene alterations. In skeletal dysplasias, TYRA-300 has demonstrated positive preclinical results and the Company expects to submit an IND for the initiation of a Phase 2 clinical study in pediatric achondroplasia in 2024.

On March 22, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported the successful dosing of first patient in the U.S. Phase I Study of TST003 (NCT05731271), its first-in-class, high affinity humanized monoclonal antibody targeting Gremlin1, for the treatment of solid tumors (Press release, Transcenta, MAR 22, 2023, View Source [SID1234629174]).

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NCT05731271 is an open-label, dose escalation, FIH study designed to evaluate the safety, tolerability, and pharmacokinetics profile of TST003 as a treatment in patients with solid tumors.

TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer.

"The enrollment and dosing of the first patient in the U.S. marks a very significant milestone for TST003: our carefully designed Phase 1 will provide the necessary clinical and translational data to achieve the full potential of targeting Gremlin1 as a single agent or in combinations with standard of care, in particular in indications with high unmet need like MSS CRC or CRPC." said Dr. Caroline Germa, Transcenta’s Executive Vice President, Global Medicine Development and Chief Medical Officer.

On March 22, 2023 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported that two preclinical studies in relation to TST003, a First-in-Class mAb Targeting GREMLIN-1, and TST010, an ADCC enhanced anti-CD25 mAb will be presented as posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, Transcenta, MAR 22, 2023, View Source [SID1234629173]). This year’s meeting will be held from April 14-19, 2023, in Orlando, Florida, USA.

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The AACR (Free AACR Whitepaper) Annual Meeting is the focal point of the cancer research community, where scientists, clinicians, other health care professionals, survivors, patients, and advocates gather to share the latest advances in cancer science and medicine from institutions all over the world.

A brief summary of the presentations is as follows:
Title: The Preclinical Characterization of TST003, a First-in-Class mAb Targeting GREMLIN-1 Overexpressed by Cancer-Associated Fibroblasts and Tumor Cells
Abstract#: 465
Session Category: Experimental and Molecular Therapeutics
Session Title: New Drug Targets
Session Date and Time: Sunday Apr 16, 2023 1:30 PM – 5:00 PM (EDT)

Title: ADCC enhanced anti-CD25 mAb (TST010) exhibited potent anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models
Abstract#: 1546
Session Category: Experimental and Molecular Therapeutics
Session Title: Antibody Drug Conjugates
Session Time: Monday Apr 17, 2023 9:00 AM – 12:30 PM (EDT)

About TST003

TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-β superfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer.

About TST010

Using immune tolerance breaking antibody platform, Transcenta generated a humanized IgG1 subtype anti-CD25 monoclonal antibody with reduced fucose (TST010). TST010 binds to human CD25 with high affinity and selectivity, but does not block IL-2 binding to CD25. Non-blocking activity to IL-2 signaling on human PBMC has been further confirmed by the phosphorylation of STAT5. By reducing fucosylation during cell culture process, TST010 mAb gains the enhanced ADCC activity in vitro and anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models.

On March 22, 2023 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that it will report full year 2022 financial results on Monday, March 27, 2023, after the close of U.S. markets (Press release, CytomX Therapeutics, MAR 22, 2023, View Source [SID1234629172]). Following the announcement, the Company will host a conference call and webcast at 5:00 p.m. ET / 2:00 p.m. PT.

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Participants may access the live webcast of the conference call from the Events and Presentations page of CytomX’s website at View Source Participants may register for the conference call here and are advised to do so at least 10 minutes prior to joining the call. An archived replay of the webcast will be available on the Company’s website.

On March 22, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported financial results for the year ended December 31, 2022 and provided a corporate update (Press release, Tempest Therapeutics, MAR 22, 2023, View Source [SID1234629171]).

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"2022 featured significant milestones for the company, including our first clinical proof of concept data, which was recognized in an oral presentation at ASCO (Free ASCO Whitepaper)," said Stephen Brady, chief executive officer of Tempest. "We were pleased to see TPST-1120 confer clinical benefit to patients, including a 30% ORR at the two highest doses in patients who had not responded to checkpoint inhibitors or who had cancer that doesn’t traditionally respond to immunotherapy. We look forward to data this year from our randomized global study with Roche in first-line liver cancer patients, as well as our second clinical program, TPST-1495, where we’ve observed disease control in late-stage cancer patients, as well as data from our exciting preclinical program targeting TREX1 in the STING pathway. 2023 is shaping up to be a data-rich year for Tempest."

2022 Accomplishments

TPST-1120 (clinical PPARα antagonist): (i) completed Phase 1 clinical study investigating TPST-1120, as a monotherapy and in combination with an anti-PD1 therapy, nivolumab, and selected recommended Phase 2 dose ("RP2D"); (ii) announced positive results including RECIST responses from the Phase 1 study in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting; (iii) presented data showing pharmacodynamic and predictive biomarkers associated with responses in cancer patients from the Phase 1 study at the 2022 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting; and (iv) continued enrollment in first-line, randomized global Phase 1b/2 study in patients with hepatocellular carcinoma (HCC), under a collaboration with F. Hoffmann La Roche.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): (i) completed enrollment in a Phase 1 study evaluating monotherapy dose and schedule optimization; (ii) continued enrollment of a study evaluating combination dose and schedule optimization with the anti-PD-1 checkpoint inhibitor, pembrolizumab; and (iii) presented preclinical data showing the superiority of targeting EP2 and EP4 together in comparison to other prostaglandin pathway approaches at both the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 and SITC (Free SITC Whitepaper) 2022.
TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): presented the first preclinical anti-tumor results with proprietary small molecule TREX1 inhibitor at AACR (Free AACR Whitepaper) 2022.
Expansion of Patent Portfolio: the U.S. Patent and Trademark Office issued a patent covering methods of treatment for our therapeutic product candidate, TPST-1495.
Planned Near-Term Milestones

TPST-1120 (clinical PPARα antagonist): we expect to (i) present new data showing an association of RECIST responses and biomarker changes at AACR (Free AACR Whitepaper) 2023; and (ii) report objective response data from up to 40 HCC patients in each arm in the first-line randomized study in the first half of 2023.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist): we plan to disclose data from (i) the Phase 1 dose escalation and schedule optimization trial studying monotherapy and combination therapy with an anti-PD1 therapy, pembrolizumab, by mid-2023, and (ii) a separate combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer in 2024.
TREX1 Inhibitor (preclinical tumor-selective STING pathway activator): we expect to present new preclinical anti-tumor results at AACR (Free AACR Whitepaper) 2023 with new proprietary small molecule series TREX1 inhibitors generated through insights resulting from human TREX1-inhibitor co-crystal structures.

Financial Results

Year End 2022

Tempest ended the year with $31.2 million in cash and cash equivalents, compared to $51.8 million on December 31, 2021. The decrease was primarily due to cash used in operations of $31.1 million, as well as $4.7 million repayment of principal on our loan, offset by net proceeds from the issuance of common stock of $8.9 million and pre-funded warrants of $7.3 million.
Net loss and net loss per share for the year were $35.7 million and $3.09, respectively, compared to $28.3 million and $7.47, respectively, for the same period in 2021.
Research and development expenses for the year were $22.5 million compared to $17.2 million for the same period in 2021. The $5.3 million increase was primarily attributable to expanded research and development efforts and higher compensation expenses due to an increase in employee headcount.
General and administrative expenses for the year were 2022 were $12.1 million compared to $9.8 million for the same period in 2021. The increase of $2.3 million was primarily due to professional and consulting fees and insurance expense.
Based on current cash position and operating plan, Tempest expects to have sufficient resources to fund operations through the second quarter of 2024.