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Item 7.01 - Regulation FD Disclosure.
Bicara Therapeutics Inc. (the “Company”) is furnishing a corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K, which the Company intends to use from time to time in meetings with investors and others beginning on January 13, 2025. The corporate presentation will also be available in the investor relations section of the Company’s website at https://ir.bicara.com/.
The information set forth under Item 7.01 and in Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01 - Financial Statements and Exhibits
(d) The following exhibits are being filed herewith:
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| 99.1 | Corporate presentation of Bicara Therapeutics Inc. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized on this 13th day of January, 2025.
| Bicara Therapeutics Inc. | ||
| By: | /s/ Claire Mazumdar | |
| Name: | Claire Mazumdar | |
| Title: | Chief Executive Officer | |
Exhibit 99.1 Fighting cancer with precision and power. Corporate Presentation | January 2025 © 2024 - 2025 Bicara Therapeutics
Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than historical factual information are forward-looking statements, including without limitation statements regarding our product development activities for ficerafusp alfa and ongoing clinical trials; the ability of clinical trials to demonstrate safety and efficacy of ficerafusp alfa; the beneficial characteristics, and the potential safety, efficacy and therapeutic effects of ficerafusp alfa; our ability to develop and advance our potential future product candidates and programs; our ability to pursue and execute our strategy for our indications, business, programs and technology; our ability to leverage existing programs and to progress additional programs, the timing of investigational new drug application submissions, our and our collaborators’ ability to protect our intellectual property for our products; our ability to enter into future license agreements and collaborations; regulatory developments; and our ability to attract and retains key scientific and management personnel. In some cases, you can identify forward-looking statements because they contain words such as “may,” “might,” “will,” “would,” “shall,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “contemplates,” “believes,” “estimates,” “looks,” “seeks,” “predicts,” “potential,” “ongoing,” or “continue” or the negative of these words or other similar terms or expressions that concern our expectations, strategy, plans or intentions, although not all forward-looking statements are accompanied by such words. Forward-looking statements are based on assumptions and assessments made by our management in light of their experience and perceptions of historical trends, current conditions, expected future developments and other factors they believe to be appropriate, and speak only as of the date of this presentation. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or other events to be materially different from any future results, performance or other events expressed or implied by the forward-looking statements. Given these uncertainties, you should not place undue reliance on forward-looking statements. Our actual future results, performance or other events may be materially different from what we expect. Except as required by law, we assume no obligation to update these forward-looking statements, or to update the reasons actual results could differ materially from those anticipated in these forward-looking statements, even if new information becomes available in the future. Factors that could cause actual results to differ from those predicted in our forward-looking statements include, among others, risks and uncertainties related to product development, including delays or challenges that may arise in the development and regulatory approval of our current and future product candidates or programs; uncertainties as to the availability and timing of results and data from preclinical and clinical studies; the timing of and our ability to submit and obtain regulatory clearance for investigational new drug applications, initiate additional clinical trials, and submit new drug applications or biologics license applications; our ability to initiate and complete our current and expected clinical trials; our ability to establish and maintain collaborations, strategic relationships and supply arrangements, or that we will not realize the intended benefits from such relationships or arrangements; whether our cash resources will be sufficient to fund our foreseeable and unforeseeable operating expenses and capital expenditure requirements; our ability to raise additional funding on favorable terms, or at all; the rate and degree of market acceptance and clinical utility of our product candidates; the ability and willingness of our third-party collaborators to continue research and, development and manufacturing activities relating to our product candidates; the accuracy of our data analyses or estimates for the potential and market for our products; our ability, and the ability of our collaborators, to protect our intellectual property and to conduct activities for the development and commercialization of our candidates in view of third party intellectual property positions; our financial performance; our ability to retain and recruit key personnel, as well as the potential contribution of our employees and board to our growth and success as a Company; developments and projections relating to our competitors or our industry; changes in general economic conditions and global instability, in particular economic conditions in the markets on which we or our suppliers operate; changes in laws and regulations; and those risks and uncertainties identified in our filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our most-recently filed Quarterly Report on Form 10-Q, and such other risks and uncertainties that may be described in subsequent filings we may make with the SEC. You should not rely upon forward-looking statements as predictions of future events or performance, or as a representation or warranty (express or implied) by us or any other person that we will achieve our objectives and plans in any specified time frame, on such specified terms, or at all. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein. Market data and industry information used throughout this presentation are based on management’s knowledge of the industry and the good faith estimates of management. We also relied, to the extent available, upon management’s review of independent industry surveys and publications and other publicly available information prepared by a number of third-party sources. All of the market data and industry information used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Although we believe that these sources are reliable as of their respective dates, we cannot guarantee the accuracy or completeness of this information, and we have not independently verified this information. Projections, assumptions and estimates of our future performance and the future performance of the industry in which we operate are necessarily subject to a high degree of uncertainty and risk due to a variety of factors. These and other factors could cause results to differ materially from those expressed in our estimates and beliefs and in the estimates prepared by independent parties. This presentation discusses potential future product candidates that are investigational only and have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these potential future product candidates for the use for which such potential future product candidates are being studied. 2
Bicara Therapeutics Investment Highlights Advancing ficerafusp alfa (FICERA) – a bifunctional EGFR-directed antibody x TGF-β ligand trap FICERA + pembro offers a potential new chemo-free 1L therapy for HPV-negative 1 R/M HNSCC that may meaningfully improve upon current standard of care FORTIFI-HN01 Ph. 2/3 trial initiated December 2024; potential accelerated approval 2 pathway based on an interim ORR analysis Significant market opportunity with ~23,000 cases of R/M HNSCC annually in the 3 U.S. and a significant unmet need for better treatment options (13% 5yr survival) Expansion into other squamous cell carcinomas and solid tumors, with encouraging 4 clinical activity observed in Ph. 1b expansion cohorts to date Seasoned management team with a strong track record of execution; robust 5 1 financial position with ~$521M in cash and equivalents 1. Cash and cash equivalents as of 9/30/24. 3 R/M HNSCC = recurrent / metastatic head and neck squamous cell carcinoma; ORR = overall response rate.
Bicara Therapeutics is led by a seasoned and driven management team Ryan Cohlhepp, Pharm.D. Claire Mazumdar, Ph.D., MBA Ivan Hyep, MBA President & Chief Operating Chief Financial Officer Chief Executive Officer Officer David Raben, M.D. Lara Meisner, J.D. Rachel Salazar, D.H.Sc. Chief Medical Officer Chief Legal Officer SVP, R&D Strategy & Operations Sathish Hasige, Ph.D. Jean-Paul Rodrique Jeltje Schulten, M.D., MBA SVP, Technical Ops & Supply SVP, Quality SVP, Clin. & Med. Affairs Chain All trademarks are the property of their respective owners. 4
Maximizing the value of FICERA across HNSCC & other solid tumors Indication Phase 1/1b Phase 2/3 Status 1L R/M Head and Neck Squamous Cell Carcinoma Pivotal Ph. 2/3: FORTIFI-HN01 – 1500mg QW (+ pembro) Trial initiated December 2024 Ph. 1b Expansion Cohort – 1500mg QW (+ pembro) Updated data expected in 1H 2025 HPV- neg Ph. 1b Expansion Cohort – 750mg QW (+ pembro) Trial ongoing Ph. 1b Expansion Cohort – CPS=0 (+ pembro) Trial ongoing HPV- HPV-Positive Smokers Ph. 1b Expansion Cohort (+ pembro) Expect to initiate trial in 1H 2025 pos Earlier-Line Head and Neck Squamous Cell Carcinoma Neoadjuvant / Locally Advanced HNSCC (combo with RT and/or anti-PD-1) Expect to initiate trial in 2025 Other EGFR+ Solid Tumors Ph. 1b Expansion: 2L+ Squamous Cancer of the Anal Canal (+ pembro) Data to be presented in Q1 2025 Ph. 1b Expansion: 2L+ Cutaneous Squamous Cell Carcinoma (monotherapy) Updated data expected in 1H 2025 Ph. 1b Expansion: 3L+ Colorectal Cancer (RAS / BRAF wild type) Expect to initiate trial in 2025 5 HNSCC = head and neck squamous cell carcinoma, QW = once weekly, CPS = combined positive score, RT = radiation therapy.
FICERA’s bifunctional design targets EGFR and TGF-β directly in the MOA TME to drive a differentiated clinical profile Action 2 Improve tolerability Trapping TGF-β 1. Improves immune response Improve anti-tumor (anti-PD-1 Synergies) activity • Relieves immune suppression • Blocks cancer associated fibroblasts, reducing fibrosis and T- cell exclusion 2. Enhances EGFR inhibition (anti- EGFR Synergies) • Prevents known EGFR resistance Action 1 mechanism (via EMT) Targeting EGFR 1. Direct anti-tumor effect • Inhibits EGFR signaling, killing cells • Maintains ADCC functionality Increase depth and 2. Drives tumor targeting duration of response • Localizes TGF-β inhibition to the TME EGFR = epidermal growth factor receptor, ADCC = antibody dependent cell-mediated cytotoxicity, TME = tumor microenvironment, 6 EMT = epithelial-mesenchymal transition
FICERA clinical biomarkers demonstrated tumor target engagement in MOA Ph. 1/1b and predicted MOA Statistically significant inhibition of tumor TGF-β observed at FICERA doses >750mg via pSMAD2 levels FICERA dose (mg QW) First definitive demonstration of pSMAD2 knockdown in patient tumors by a TGF-β inhibitor 7
Dose FICERA dose expansion strategy driven by strong biologic rationale for Expansion the dual inhibition of both EGFR and TGF-β Dose Expansion FICERA monotherapy EGFR 2L+ CSCC Overexpression n = 12 + 25* FICERA – 1500mg QW Based on preliminary efficacy and safety & tolerability data, 1500mg QW FICERA was chosen as FICERA + PEMBRO recommended dose to take into dose expansion cohorts R/M 1L HNSCC MTD was not reached n = 13+ 26* Role 2L+ SCAC of TGF-β FICERA – 1500mg QW Enrollment complete *Simon 2-stage design 8 MTD = Maximum Tolerated Dose
Market HNSCC is a common cancer with significant unmet need for improved Opportunity treatment options that extend survival Overview of head & neck cancers ~67,000 • Head and neck cancer accounts for ~4% of all cases of HNSCC each year in the U.S. cancers in the U.S. • Squamous cell carcinomas represent ~90% of 10% ~30% H&N metastatic at metastases diagnosis eventually • Oropharyngeal lesions are typically tested for HPV § HPV-positive caused by HPV infection § HPV-negative typically caused by smoking and ~23,000 chewing tobacco represents 80% of HNSCC in the R/M setting and carries a worse cases of R/M HNSCC each year in the U.S. prognosis vs. HPV-positive • Treatment decisions are guided by CPS or PD-L1 ~12 months 13% expression and options are limited to cetuximab, median survival 5-year survival anti-PD1, chemotherapy Sources: Cancer.net, Cleveland Clinic (2022); SEER 2012-2018 data; Cerner (2022); Bedi et al. Mol Cancer Ther. 2012; Acta Otorhinolaryngol Ital. 2020, KeyNote-048 ph.3 trial; ASCO (2022); DRG HNSCC (2019) 9
Market The patient journey in HNSCC Opportunity Symptoms 1 Relapse 4 LA HNSCC Patient presents to primary care/ENT with symptoms: 50% Relapse within 2 years Pain, swallowing difficulty, mucosal 1 after treatment for LA HNSCC bleeding, asthenia, weight loss Testing and Staging 2 Work-up may include: 1L R/M HNSCC Metastatic Laryngoscopy, biopsy, imaging (CT at diagnosis scan, MRI) HPV/p16 testing in Oropharynx CPS = 0 CPS≥1 Diagnosis of cancer MDT & Treatment 3 Platinum-based + cetuximab Pembrolizumab mono Multi-disciplinary (med-onc, rad- 2 onc, surgeon) decision: Study Platinum + 5FU + Pembro Locally Advanced HNSCC: Curative-intent surgery and/or Study chemo-radiation M1 disease: palliative treatment & Molecular testing: PD-L1 CPS Initial focus 1. HNSCC population who relapse <6 months after CRT receive nivolumab as 1L treatment 2. Choice of pembro + chemo (platinum + 5FU) is at the physician’s discretion and is typically more common in the CPS<20 group and/or rapidly progressing disease. LA = Locally advanced 10
Market HNSCC patients suffer significant symptomology and represent a major Opportunity unmet need Patients experience acute and chronic toxicities after surgery and/or chemo-radiation Acute side effects Chronic side effects • Painful sores in the mouth or throat (oral • Trismus – difficulty opening the jaw / nerve mucositis) and dermatitis damage to jaw • Difficulty swallowing (dysphagia) from surgery • Osteoradionecrosis – breakdown of the or chemo-RT mandible • Feeding tube may be required for nutritional • Radiation based fibrosis causing tissue support during Chemo-RT for many patients damage • Dry mouth (xerostomia) • Neuropathies from surgery/chemotherapy and radiation • Speech/voice difficulties and managing the stoma after laryngectomy • Lymphedema (tissue swelling) • Nutritional deficits Source: Head and Neck Cancer Alliance. Chemo-RT = chemoradiotherapy 11
FICERA + pembro R/M HNSCC expansion cohort based on mechanistic 1L HNSCC synergies with anti-PD-1 and IST precedent Two ISTs exploring anti-PD-1 + cetuximab help inform FICERA registration path 1 Study KEYNOTE-048 Sacco, et al 2021 Chung, et al 2022 Action 2 Published Trapping TGF-β Pembro Cetux + pembro Cetux + nivo Drug(s) Phase 3 Phase 2 Phase 1/2 Phase 1. Improves immune response (anti-PD-1 Synergies) N=33 N=43 Size N=257 • Relieves immune suppression Randomized, open-label, Open-label, single- Open-label, single- Design three-arm study arm arm • Blocks cancer associated Efficacy Metrics fibroblasts, reducing fibrosis and T-cell exclusion 19% 48% 37% ORR CRR 5% 3% 2% 3.2 months 6.5 months 6.2 months mPFS mOS 12.3 months 18.4 months 20.2 months 1. Data shown only for patients with CPS ≥ 1 treated with pembrolizumab monotherapy. All trademarks are the property of their respective owners. 12
FICERA + pembro demonstrates compelling activity and depth of 1L HNSCC response in 1L R/M HNSCC regardless of HPV status FICERA + pembro expansion in R/M HNSCC • Population § 1L R/M HNSCC § Oral cavity, oropharynx, hypopharynx & larynx § HPV testing required for oropharyngeal cancer § CPS≥1 • 54% (21/39) ORR in CPS≥1 patients 1 § Historical pembro mono ~19% ORR • 15% (6/39) CR Rate in CPS≥1 patients § 4 additional patients with -100% PRs** Note: Out of 42 patients, 3 patients were non-efficacy evaluable. Best overall response (investigator-assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1). CPS=combined positive score, CR=complete response, DCR=Disease Control Rate, HPV=human papilloma virus, ORR=Overall response rate, PR=partial response, uPR=unconfirmed partial response, SD=stable disease ** May still have nodal disease 1. Based on historical data. No head-to-head studies have been conducted. 13
Market HPV-negative R/M HNSCC: a challenging tumor type associated with Opportunity overexpression of EGFR and TGF-β HPV-negative disease demonstrates Overexpression of EGFR and TGF-β in HNSCC distinct biological and mutational features correlated with a poor prognosis • HPV-negative disease is etiologically distinct from HPV-positive disease and associated with: § Increased EGFR expression compared to HPV- positive HNSCC patients § Elevated levels of TGF-β1 in serum § High rate of therapeutic resistance (including to anti-PD-1 checkpoint inhibitors) § High tumor burden and symptomatic disease Source: Bedi, Atul, et al. Molecular cancer therapeutics (2012). 14 Log2(EGFR_FKPM+1)
FICERA + pembro demonstrates significantly improved activity and 1L HNSCC depth of response in HPV-negative CPS≥1 1L R/M HNSCC In HPV-negative patients: • 64% (18/28) ORR observed, CPS≥1 patients 1 § Historical pembro mono expected to be ~19% ORR § 15/18 confirmed responses • High response rates in subgroups that are typically refractory to checkpoint therapy: § 70% (14/20) ORR in patients with locoregional disease involvement § 54% (7/13) ORR in CPS low (1-19) • 18% (5/28) Complete Response (CR) rate § Pembro and pembro + cetux have 1 historically achieved a ~3-5% CR rate Note: Best overall response (investigator-assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1). CPS=combined positive score, CR=complete response, DCR=Disease Control Rate, HPV=human papilloma virus, ORR=Overall response rate, PR=partial response, uPR=unconfirmed partial response, SD=stable disease 1. Based on historical data. No head-to-head studies have been conducted. 15
HPV-negative 1L HNSCC suggests improved median PFS over pembro 1L HNSCC monotherapy supportive of TGF-β hypothesis • Median PFS of 9.8 months in HPV-negative subgroup § 57% (16/28) of pts with PFS>6 months • Median duration of response (DOR) not yet reached • Median overall survival (OS) not yet reached Historical data for pembrolizumab in this population (KEYNOTE-048): 1 mPFS : 3.2 mo (HPV-pos & HPV-neg) 1. Based on historical data. No head-to-head studies have been conducted. 16
1L HNSCC FICERA has been generally well-tolerated with no treatment-related deaths Most common (>10%) related adverse events – summary by preferred term and maximum grade All 1L R/M HNSCC subjects received 1500mg QW and Pembrolizumab (n=42) All Grade Grade FICERA + pembro in 1L R/M HNSCC Preferred term Grades 3-4 5 safety profile: Any Related AE 40 (95%) 17 (40%) 0 (0%) Dermatitis acneiform 32 (76%) 5 (12%) 0 (0%) • EGFR-related AEs: Fatigue 18 (43%) 2 (5%) 0 (0%) § 76% had dermatitis acneiform, majority are Pruritus 17 (40%) 0 (0%) 0 (0%) Anaemia 15 (36%) 6 (14%) 0 (0%) Grade 1-2 in severity Hypophosphataemia 16 (38%) 0 (0%) 0 (0%) • Hypothesized TGF-β-related AEs: Hypomagnesaemia 15 (36%) 0 (0%) 0 (0%) Dry skin 13 (31%) 0 (0%) 0 (0%) § Nearly all AEs were transient Grade 1-2 local Stomatitis 10 (24%) 1 (2%) 0 (0%) mucosal bleeds or epistaxis Infusion related reaction 8 (19%) 1 (2%) 0 (0%) Hypokalaemia 8 (19%) 0 (0%) 0 (0%) • No treatment related deaths were reported Nausea 7 (17%) 0 (0%) 0 (0%) Proteinuria 7 (17%) 0 (0%) 0 (0%) Epistaxis 6 (14%) 0 (0%) 0 (0%) Lipase increased 6 (14%) 0 (0%) 0 (0%) Skin fissures 6 (14%) 0 (0%) 0 (0%) Decreased appetite 6 (14%) 1 (2%) 0 (0%) Headache 5 (12%) 1 (2%) 0 (0%) Rash maculo-papular 5 (12%) 1 (2%) 0 (0%) Diarrhoea 5 (12%) 0 (0%) 0 (0%) Aspartate aminotransferase increased 5 (12%) 0 (0%) 0 (0%) Gingival bleeding 5 (12%) 0 (0%) 0 (0%) 17
FICERA 1L HNSCC Ph.1b expansion supports a pivotal trial with path to 1L HNSCC accelerated approval FICERA has demonstrated a strong clinical profile • 64% ORR in HPV-negative, CPS≥1 R/M HNSCC in combination with pembro vs. ~19% 1 historical pembro monotherapy • 18% complete response rate vs. ~3-5% with available therapies (pembro and pembro + cetux) • mPFS of 9.8 months (vs. 3.2 months for pembro monotherapy in HPV+/-) • Generally well tolerated safety profile FORTIFI-HN01 Ph. 2/3 trial initiated December 2024 FDA feedback supports potential accelerated approval pathway 1. Based on historical data. No head-to-head studies have been conducted. 18
FORTIFI- FORTIFI-HN01 Phase 2/3 trial design allows for efficient path-to-market HN01 Potential Potential Accelerated Approval Full Approval Interim Analysis Endpoint: Endpoint: Dose Selection ORR (primary) OS (primary) FICERA 1500mg QW + Pembro 200mg Q3W FICERA optimal dose R/M HNSCC + FICERA 750mg QW Pembro 200mg Q3W 1L Setting + R CPS ≥ 1 Pembro 200mg Q3W excl. HPV-positive OPSCC Pembro 200mg Q3W Design Total Sample Size Interim Analysis 1 n ~ 60 (Dose Optimization) Interim Analysis 2 (ORR) n ~ 415 Primary Analysis (OS) n ~ 650 Anticipated data availability are based on current expectations and may be subject to delay. 19
FORTIFI- Seamless design in FORTIFI-HN01 expedites timelines to potential HN01 approval Ph. 2/3 FORTIFI-HN01 is designed such that patients enrolled in dose selection at the optimal dose will contribute to the final efficacy analyses, while those at the non-optimal dose will not Enrollment not stopped; Approximate # of Patients Time for follow-up and Enrolled In Each Arm regulatory interaction Switch from 1:1:1 to 2:1 randomization Optimal FICERA Dose 10 20 40 60 100 150 ~200 ~360 Non-Optimal Dose arm dropped. Non-Optimal Patients enrolled in this arm do not contribute FICERA Dose 10 20 40 60 to primary efficacy analysis of Ph. 3 (ORR/OS) Pembro control 10 20 40 60 90 115 ~140 ~220 ~LPI for Dose Dose Selection ~LPI for ORR ~LPI for OS Selection Decision Made Analysis Analysis Enrolling & contribute to final ORR / OS Enrolling but do NOT contribute to final ORR / OS Enrolling & contribute to final ORR / OS 1. Dose selection will be made after the first ~10-20 patients in each dose arm have at least 12-weeks of follow up. At the time of dose selection, it is estimated that ~60-100 patients in each dose arm will have been enrolled in the non-optimal dose arm and will not contribute to the efficacy analyses of the Ph. 3 trial. LPI = last patient in. 20
Dose Proposed OBD data package will include data from both Ph1b and Ph2/3 Selection studies Based on FDA feedback, team will request a Type D meeting to seek agreement on the dose to carry forward 1 N = 30 FICERA dose 1500mg >2 years follow up Ph. 1/1b selection: QW Extended (n=39) Dose Expansion safety & ~ 40-50 patients informing N ~ 30 Ongoing & durability 750mg selection across both dose >1 year follow up New Dose Expansion QW options Cohort (n~30) ~ 30 patients at each dose N = 10-20 N = ~60-80 2 with > 1 year of follow up to with 12 weeks FU enrolled 1500mg capture durability QW Randomized Ph. 2/3 N = 10-20 safety & N = ~60-80 Data package will include FORTIFI-HN01 2 with 12 weeks FU enrolled efficacy 750mg updated popPK, exposure- QW response analysis, safety, efficacy, and durability 1. In Ph. 1/1b dose expansion, of the n=42 patients across HPV-negative and HPV-positive, the n=30 HPV-negative patients will inform dose selection. 2. Dose selection will be made after the first ~10-20 patients in each dose arm have at least 12 weeks of follow up. At the time of dose selection, it is estimated that ~60-80 patients in each dose arm will have been enrolled, and thus those patients in the non-optimal dose arm will not contribute to the efficacy analyses of the trial. Anticipated data availability are based on current expectations and may be subject to delay. OBD = optimal biological dose. FU = follow up. PopPK = population pharmacokinetics. 21
LA HNSCC Advancing to earlier stages of HNSCC represents a Opportunity significant opportunity for FICERA expansion opportunity Relapse LA HNSCC 50% Relapse within 2 years 1 after treatment for LA HNSCC >60K cases / year in U.S. 1L R/M HNSCC Metastatic at diagnosis Recurrent / Metastatic CPS = 0 CPS≥1 HNSCC Platinum-based + cetuximab Pembrolizumab mono 2 Study Platinum + 5FU + Pembro Study 22
LA HNSCC Most HNSCC patients are diagnosed with locally advanced (LA) HNSCC Opportunity Strong rationale to explore FICERA in LA-HNSCC Standard-of-care HNSCC disease stage 2,3 Stage 2,3 treatment 1 at diagnosis 60% 30% Locally Treatment goals for 30% Radiotherapy or surgery Early stage advanced patients with LA HNSCC, Early stage (Stage 0–II) treated with curative 2,3,8-11 intent, include: Surgery ± CRT or 60% Ÿ Cure CRT, or Locally advanced cetuximab + RT or RT (Stage III–IVB) Ÿ Long term survival Ÿ Locoregional control (LRC) 10% pembro ± CT or 10%Ÿ Organ preservation Metastatic cetuximab + CT or CT Metastatic Ÿ Quality of life alone or BSC (Stage IVC) FICERA has strong biologic rationale to deliver on treatment goals of LA HNSCC 12 1) Targeting TGF-β in LA setting: radiation therapy associated with increases in TGF-β ; target resistance early and reduce scarring / fibrosis in normal tissue for organ preservation and improved quality of life 2) Cetuximab precedent in combination with RT for unresectable, cisplatin-ineligible patients; improve long-term survival and LRC 1. Corvò R. Radiother Oncol. 2007 Oct;85(1):156-70; 2. NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers V3.2021; 3. Machiels JP, et al. Ann Oncol 2020;31:1462–1475; 4. Bray FF, Pisani P, Parkin DM. GLOBOCAN 2002: Cancer Incidence, Mortality and Prevalence Worldwide. IARC Cancer Base No. 5. version 2.0. Lyon: IARC Press; 2004. http://www-dep.iarc.fr; 5. Seiwert et al. Nature Clinical Practice Oncology, March 2007; Vol 4 No. 3 (The chemoradiation paradigm in head and neck cancer); 6. Bernier J, et al. N Engl J Med 2004;350:1945–1952; 7. Cooper JS, et al. N Engl J Med 2004;350:1937–1944; 8. Lo Nigro C, et al. Cancer Manag Res 2017;9:363–371; 9. Ang KK. Oncologist 2008;13:899–910; 10. Haigentz M Jr, et al. Expert Opin Pharmacother 2010;11:1305–1316; 11. Haddad RI, et al. Ann Oncol 2018;29:1130–1140; 12. Centurione, L., et al. (2016). Frontiers in Oncology, 6, 175 OBD = optimal biological dose. FU = follow up. 23
Beyond Plan to expand FICERA to additional tumor types where there is strong HNSCC biologic rationale and / or early signals of activity Other Solid Tumors / Squamous Cell Carcinomas FICERA monotherapy: 42% ORR across n=12 patients in 2L+ post-PD-1 Potential expansion to areas of EGFR / TGF-β involvement: • Cutaneous squamous cell carcinoma (cSCC) – preliminary 42% ORR (5/12) in 2L+ PD-1- refractory with FICERA monotherapy • Colorectal cancer (CRC) – cetuximab precedent • Squamous cancer of the anal canal (SCAC) – data to be presented at a medical meeting in Q1 2025 24
CRC Expansion to 3L+ MSS RASwt metastatic colorectal cancer (mCRC) Initial Ph. 1/2 Proof of Concept Study Expansion to mCRC Unresectable mCRC • EGFR an established target in mCRC FICERA • 2-3 previous lines N = ~20 in Stage 1 • Ability to target TGF-β driven resistance to • Anti-EGFR is not the last EGFR targeted therapies line of treatment • Received prior biologics • Initial late-line development strategy i.e. anti-VEGF 1 supported by clinical evidence of activity of EGFR-rechallenge in wtRAS CRC • Confirmed RAS/BRAF wt population and MSS FICERA + pembro • ECOG 0-1 • Rationale to combine TGF-β inhibition with N = ~20 in Stage 1 immunotherapy to address overlapping but non-redundant tumor survival mechanisms Primary goals: evaluate safety, tolerability, and initial efficacy (ORR/DCR). Potential to expand cohorts to n~50 in each arm in Stage 2. 1. Sartore-Bianchi, Andrea, et al. Nature Medicine 28.8 (2022): Bev: bevacizumab (Avastin); mCRC: metastatic colorectal cancer; MSS: microsatellite stable; ORR: objective response rate; Q2W: dosed every 25 2 weeks Randomized 1:1
Bicara Therapeutics is poised to establish FICERA + pembro as a new At a Glance potential therapy for 1L HPV-negative R/M HNSCC Focus Key Achievements Showed strong clinical activity of FICERA in combination with pembro in HPV-negative 1L ü R/M HNSCC (64% ORR, 18% CRR, 9.8mos PFS) Clinical Demonstrated activity of FICERA in other squamous cell carcinomas and solid tumors ü Aligned on registration-enabling Ph. 2/3 trial design and established a clear path to FDA ü Regulatory approval based on OS, with potential for an accelerated approval upon an interim analysis based on ORR Initiated FORTIFI-HN01, a pivotal Ph. 2/3 trial in HPV-negative 1L R/M HNSCC in ü FORTIFI-HN01 December 2024 1 Robust financial position with ~$521M in cash and cash equivalents , including ~$362M ü Financial in gross proceeds from upsized IPO 1. Cash and cash equivalents as of 9/30/24. 26