Full Press Release Details
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- 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
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- directly
in the MOA TME to drive a differentiated clinical profile Action 2 Improve tolerability Trapping TGF- 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- 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- observed at FICERA doses >750mg via pSMAD2 levels FICERA dose (mg QW) First definitive demonstration of pSMAD2 knockdown in patient tumors by a TGF-
Dose FICERA dose expansion strategy driven by strong biologic rationale
for Expansion the dual inhibition of both EGFR and TGF- 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- FICERA - 1500mg QW Enrollment complete *Simon 2-stage design 8 MTD = Maximum Tolerated
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
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
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- 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- HPV-negative disease demonstrates Overexpression of EGFR and TGF- 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- 1 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.
HPV-negative 1L HNSCC suggests improved median PFS over pembro 1L HNSCC
monotherapy supportive of TGF- 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- -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%)