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MHNCS 2026 Clinical Update February 20, 2026 FICERA: enabling tumor penetration to drive deep and durable responses in HPV-neg HNSCC
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Forward-looking statements 2 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 clinical development of ficerafusp alfa in combination with pembrolizumab in 1L HPV-negative R/M HNSCC, including anticipated safety, efficacy, and depth and durability of responses; the potential of a loading and maintenance dosing regimen, including plans for an additional study and potential future regulatory alignment for this alternative dosing regimen; the ongoing enrollment and advancement of the Phase 2/3 FORTIFI-HN01 clinical trial; expectations for the potential U.S. approval and launch of ficerafusp alfa; and the commercial opportunity for ficerafusp alfa, including its potential to become a new standard of care for 1L HPV- negative R/M HNSCC. 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.
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Agenda & today’s presenters 3 Claire Mazumdar, Ph.D., MBA Chief Executive Officer MHNCS 2026 Clinical Update 2 Preliminary safety & efficacy data for 2000mg Q2W FICERA + pembro Less Frequent Dosing Strategy for FICERA 3 Contextualizing 2000mg Q2W dose and impact on strategy 1 Ficerafusp alfa (FICERA) in 1L R/M HPV-Negative HNSCC First and only EGFR x TGF-β bifunctional antibody HNSCC = head and neck squamous cell carcinoma; EGFR = epidermal growth factor receptor; TGF = transforming growth factor; QW = dosed weekly Joining for Q&A Ryan Cohlhepp, Pharm.D. President & Chief Operating Officer Tanya Green Chief Development Officer Bill Schelman, MD, Ph.D. Executive Vice President, Clinical Development
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Ficerafusp Alfa (FICERA) in 1L R/M HPV-Negative HNSCC First and only EGFR x TGF-β bifunctional antibody 4
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5 FICERA – the first and only bifunctional EGFR-directed antibody combined with a TGF-β ligand trap designed to drive tumor penetration Inadequate tumor penetration has challenged the treatment of many solid tumor cancers, including HPV- negative R/M HNSCC FICERA was specifically designed to enable tumor penetration and drive deep, durable responses to yield improved outcomes and survival Targeting EGFR 1. Direct anti-tumor effect 2. Drives tumor targeting 1 2 Trapping TGF-β 1. Enables tumor penetration 2. Prevents resistance
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HPV-negative ~54%* 21% 21.7 months* NA 6 FICERA’s clinical profile meaningfully improves outcomes compared to standard of care 6 Based on historical published data. No head -to-head studies have been conducted, and cross -trial comparisons may not be reliable due to differences in molecule composition, trial design, and patient population and characteristics. *HPV -negative R/M HNSCC patients only (CPS ≥ 1). 1. Burtness B. et al. Lancet. 2019;394:1915 –28. 2. Vasiliadou I, et al. Int J Cancer. 2024;155(5):883-93. 3. Black CM, et al. Front Oncol. 2023;13:1160144. 4. Chung et al. ASCO 2025. ~3X increase in ORR vs. pembro alone >3X increase in mDOR vs. pembro + chemo >2X increase in mOS vs. pembro +/- chemo HPV-all comers KEYNOTE-0481 ORR 19% 36% CR 5% 7% mDOR 23.4 months 6.7 months mOS 12.3 months 13.6 months Pembrolizumab Pembrolizumab + Chemo HPV-negative Real World Data2,3 mOS 9 months 7 months FICERA (1500mg QW)* + pembro4 21.3 months*
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7 FICERA’s tumor penetration was designed to drive durability Median Duration of Response: Pembro Combinations in 1L R/M HNSCC HPV-All HPV-Negative Median DOR (Months) FICERA 1500mg + pembro 21.7 months in HPV-negative 2 6 10 14 18 22 4 8 12 16 20 240 Pembro + chemotherapy Pembro + lenvatinib Pembro + cetuximab Pembro + petosemtamab Non-Tumor Penetrant (Chemo / EGFR) Responses 6.7 months 10.1 months 13.1 months ~11.0 months* Tumor Penetrant (PD-1 / FICERA) Responses Based on historical published data. No head -to-head studies have been conducted, and cross -trial comparisons may not be reliable due to differences in molecule composition, trial design, and patient population and characteristics. Sources: KN -048: Burtness, Barbara, et al. The Lancet 394.10212 (2019): LEAP -010: Licitra et al. MHNCS 2024, 18(5) Abs 1; Sacco, et al. The Lancet Oncology 22.6 (2021): 883 -892; Chung et al. ASCO 2025. *Pembro + petosemtamab mDOR reported as of 9/16/24 data cutoff: Van Herpen, Carla ML, et al. (2025).
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CPS, combined positive score; Q3W, every three weeks; ORR, objective response rate; DOR, duration of response; PFS, progressi on-free survival; pembro, pembrolizumab 1. Chung et al. ASCO 2025; 2. Kaczmar et al. ESMO Asia 2025 8 Pivotal FORTIFI-HN01 trial design has enabled accelerated dose selection and efficient Phase 3 initiation Phase 1b Phase 2 Phase 3 Open-label safety and dose selection Blinded safety and efficacyBlinded safety, efficacy, and dose selection FICERA 1500mg QW + 200mg pembro Q3W Pembro 200mg Q3W FICERA 750mg QW + 200mg pembro Q3W FICERA 1500mg QW + 200mg pembro Q3W1 FICERA 750mg QW + 200mg pembro Q3W2 1:1:1 2:1 Primary endpoints: ORR, OS Secondary endpoints: DOR, PFS, safety Additional cohorts allow for: • Less frequent dosing for 1L R/M HNSCC to support commercialization efforts • HNSCC market opportunity expansion Drop 750mg QW arm in Phase 3 and move to 2:1 randomization Phase 3 initiated and currently enrolling with 1500mg QW FICERA • Patients enrolled at 1500mg FICERA QW in the Phase 2 portion continue treatment and contribute to pivotal efficacy analysis FORTIFI: seamless registration -enabling Phase 2/3 study
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MHNCS 2026 Clinical Update Preliminary safety & efficacy data for 2000mg Q2W FICERA + pembro 9
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10 Baseline Characteristics Data snapshot: December 16, 2025. CPS = combined positive score; DM = distant metastatic; ECOG = Eastern Cooperative Oncology Group; HNSCC = head and neck squa mous cell carcinoma; HPV = human papillomavirus; LR = locoregional; R/M = recurrent or metastatic. Characteristic Safety set (N=30) Age Median (range) 63 (28-84) Sex – n (%) Male/Female 67% / 33% Primary disease site – n (%) Oropharynx (HPV-neg) 6 (20%) Oral Cavity 19 (63%) Hypopharynx 2 (7%) Larynx 3 (10%) CPS – n (%) 1-19 15 (50) ≥20 15 (50) Locoregional (LR) vs distant metastatic (DM) disease – n (%) LR only 19 (63%) LR + DM 6 (20%) DM only 5 (17%) Sum (mm) of target lesion diameters – % Median 33 > 50 37% > 70 23% ECOG performance status – % 0 vs.1 33% / 67% Population • 1L R/M HNSCC, HPV-Negative • Oral cavity, oropharynx, larynx, and hypopharynx • CPS ≥1 • ECOG performance status 0-1 Patient demographics and baseline characteristics FICERA 2000mg Q2W + pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC
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11 Safety Data snapshot: December 16, 2025 *There was 1 Grade 4 event of hypokalemia; there were no Grade 5 events 1. Related TEAEs are those with relationship of “Poss ibly Related”, “Probably Related”, and “Definitely Related” to ficerafusp alfa considered by the investigator. They also include TEAEs with missing drug relationships, which is treated as “Possibly Relate d”. AE = adverse event; TEAE = treatment -emergent adverse event; TRAE = treatment related adverse event. FICERA continues to exhibit a generally well-tolerated safety profile FICERA 2000mg Q2W + pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC 2000mg Q2W FICERA + pembrolizumab safety profile: • The combination was tolerable with a manageable safety profile* • No treatment-related deaths were reported • Safety profile at 2000mg Q2W was consistent with established safety profile of 1500mg FICERA + pembrolizumab in R/M HNSCC Preferred term, n (%) Safety set (N=30) Any grade Grade 3 Grade 4 Grade 5 Any TEAE 29 (97%) 16 (53%) 1 (3%) 0 Dermatitis acneiform 24 (80%) 3 (10%) 0 0 Anemia 14 (47%) 8 (27%) 0 0 Fatigue 12 (40%) 1 (3%) 0 0 Epistaxis 12 (40%) 0 0 0 Stomatitis 11 (37%) 3 (10%) 0 0 Pruritus 11 (37%) 1 (3%) 0 0 Headache 10 (33%) 0 0 0 Nausea 9 (30%) 1 (3%) 0 0 Dry skin 9 (30%) 0 0 0 Skin fissures 7 (23%) 0 0 0 Infusion-related reactions 7 (23%) 0 0 0 Hypophosphatemia 6 (20%) 0 0 0 Hypomagnesemia 6 (20%) 0 0 0 TRAE leading to ficerafusp alfa discontinuation 3 (10%) Most frequently reported (≥20%) TEAEs related 1 to FICERA
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12 Efficacy Data snapshot: December 16, 2025. Investigator -assessed best overall response per RECIST 1.1. HPV-negative efficacy-evaluable population (N=27). ORR = objective response rate; CR = complete response; PR = partial response; SD = stable disease; SLD = sum of target lesion diameters (mm); PD = progressive disease • Confirmed ORR: 48% (13/27) ▪ Disease Control Rate: 8 5% (23/27) • Deep Responses: 77% (10/13) of responders achieved ≥ 80% tumor shrinkage ▪ CR rate: 26% (7/27) • Rapid Responses ▪ Median time to response: 1.6 months ORR % (N) CPS CPS 1-19 57% (8/14) CPS ≥ 20 39% (5/13) Tumor Burden (SLD) ≤ 50mm 53% (9/17) > 50mm 40% (4/10) > 70mm 33% (2/6) Activity Across Patient Subgroups Preliminary efficacy data demonstrated rapid, deep responses FICERA 2000mg Q2W + pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC −100 −80 −60 −40 −20 0 40 80 100 20 Best change from baseline (%) 60 SD * SD SDPR SDSDSD * SD * PDPDPD * PD CR CR * CR * CR * CRCR * CRPR * PRPR * SD SD SD * PR * PR * Deep PR / CR With ≥ 80% Shrinkage PR With < 80% Shrinkage SD PD * CPS 1-19
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13 Efficacy Preliminary efficacy data demonstrated enhanced durability FICERA 2000mg Q2W + pembrolizumab in HPV-neg, CPS≥1 1L R/M HNSCC confirmed responders Data snapshot: December 16, 2025. Investigator -assessed best overall response per RECIST 1.1. *Deep response refers to ≥ 80% tumor shrinkage from baseline
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14 Efficacy By Dose Data snapshot: December 16, 2025. *Data snapshot: July 9, 2025, Kaczmar, JM, et al. Ann Oncol. 2025;36(Suppl 4):667O . †Data snapshot: March 20, 2025. Chung CH, et al. J Clin Oncol. 2025;43(16 suppl):6017. HPV -negative efficacy-evaluable population. Investigator -assessed best overall respons e per RECIST 1.1. #Deep response refers to ≥ 80% tumor shrinkage from baseline. EE = efficacy evaluable; ORR = objective response rate; CR = co mplete response. NE = not estimable. FICERA clinical experience across Phase 1b cohorts FICERA 2000mg Q2W, 1500mg QW, and 750mg QW in HPV-neg, CPS≥1 1L R/M HNSCC 2000mg Q2W 1500mg QW† 750mg QW* Metric EE set (N=27) EE set (N=28) EE set (N=30) Confirmed ORR % (N) 48% (13/27) 54% (15/28) 57% (17/30) CPS 1-19 57% (8/14) 54% (7/13) 73% (8/11) CPS ≥ 20 39% (5/13) 53% (8/15) 47% (9/19) CR Rate % (N) 26% (7/27) 21% (6/28) 10% (3/30) Deep Responses# % (N) 77% (10/13) 80% (12/15) 29% (5/17) Median PFS NE 9.9 months NE Median DoR NE 21.7 months NE Median OS NE 21.3 months NE Median Time to Response 1.6 months 1.4 months 1.6 months • Consistent safety, efficacy, depth of response, and rapid time to response justifies further exploration for less frequent dosing schedule • Data further increase confidence in the pivotal study Phase 1b data from exploratory higher dose, less frequent regimen Phase 1b data from dose selected for pivotal study
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Less Frequent Dosing Strategy for FICERA Contextualizing 2000mg Q2W dose and impact on strategy 15
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16Bicara Therapeutics data on file. Plots show mean with SEM. pSMAD2 Analysis: N=5 samples at 750mg, N=7 samples at 1500mg N=4 samples at 2000mg. Immune -activation cytokine analysis: N=24 samples for 750mg (except N=25 for CXCL10), N=27 for 1500mg, and N=11 for 2000mg (except N=12 for CXCL10). Blood FICERA plus pembrolizumab maintains TGF -β inhibition and immune activation at a higher and less frequent (2000mg Q2W) dose, supporting development of less frequent dosing regimen Increased Immune-Activation at 1500mg QW and 2000mg Q2W pSMAD2 Tumor tissue Increased TGF-β Inhibition at 1500mg QW and 2000mg Q2W TNFA IFNG CXCL9 CXCL10 TGF-β inhibition is maintained with less frequent dose of FICERA
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17 ** Patient with complete response at 2000mg Q2W Predose Week 3 CD8+ Predose Week 3 Patient with 58% tumor reduction at 2000mg Q2W CD8 T-Cells (paired biopsies) at 2000mg Q2W FICERA plus pembrolizumab TGF-β inhibition with FICERA drives tumor penetration of T-cells at less frequent dose Bicara Therapeutics data on file. CD8 T -cells analysis N=6 pairs. **p<.01 paired t -test Predose Week 3
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-63% 27% -82% 64% -100% 73% 750 mg QW (n=15) 1500 mg QW (n=11) 2000 mg Q2W (n=11) 18 Bicara Therapeutics data on file. TME = tumor microenvironment. *Median depth of response represents the median of the best percent change from baseline amongst the confirmed responders at 24-weeks follow-up. Median Depth of Response* % Of Responders Achieving Deep (≥80%) Response Depth of Response At 24-Weeks Observed trends of higher TGF-β inhibition within the TME at higher doses, even at a less frequent dose of FICERA Increases in TGF-β inhibition directly in the TME enable greater tumor penetration to drive deeper and more durable responses FICERA’s TGF-β inhibition and tumor penetration are observed at higher doses with deeper responses
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19 Key principles guiding less frequent dose exploration for FICERA Mechanistic Differentiation Maintain FICERA’s hallmark TGF-β inhibition at a less frequent dose while being responsive to the tumor as it shrinks Meaningful Clinical Efficacy Rapid and deep responses that yield durability and long-term outcomes due to TGF-β inhibition Patient Optionality Enhance convenience and patient flexibility by offering less-frequent dosing option in combination with pembrolizumab
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20 Totality of data support a loading and Q3W maintenance regimen for FICERA Mechanistic Differentiation Rapid tumor penetration and shrinkage with TGF -β targeting creates a natural opportunity to extend the dosing interval while preserving potency**** * N=16 N=12 N=13 N=7 **** TGF-β neutralization (plasma) at 2000mg Q2W FICERA plus pembrolizumab ****p<.0001;***p<.001, ** p<.01, *p<.05 Bicara Therapeutics data on file. Meaningful Clinical Efficacy Integrated clinical and PK/PD modeling data support that deep, durable responses can be maintain with loading and maintenance Advancing a Loading + Q3W Maintenance Strategy Finalizing the optimal loading schedule and maintenance dose to align with regulators; no change to ongoing Phase 3 FORTIFI -HN01 study of 1500mg QW, but aim to have loading and maintenance data in hand by potential approval
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21 2000mg Q2W data further FICERA differentiation Observed consistent, generally well -tolerated safety and rapid, deep responses at 2000mg Q2W FICERA Deep responses trend toward more durable responses, longer PFS, and prolonged OS Sustained TGF-β inhibition, immune activation, tumor penetration, and deep responses observed at 2000mg Q2W FICERA, supporting development of less frequent dosing regimen Growing body of PK, translational, and clinical data support a loading and Q3W maintenance regimen to optimize efficacy, safety, and schedule; pursuing regulatory alignment with aim to generate data in time for potential US launch Expanding data set reinforces established clinical differentiation Pursuing less frequent dosing for optionality, convenience
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Thank You