Financial Data and Key Metrics Changes - Revenue for Q4 2024 was $7.4 million, entirely from the Sanofi collaboration [36] - R&D expenses for the quarter were $71.8 million, with adjusted cash R&D spend of $65 million reflecting a 23% sequential increase from Q3 [37] - G&A expenses were $16.3 million, with adjusted cash G&A spend of $9.3 million, up 13% sequentially [37] - Cash balance at the end of 2024 was $851 million, providing a runway into mid-2027 [38] Business Line Data and Key Metrics Changes - The company is focused on advancing its immunology pipeline, particularly with the STAT6 and TYK2 programs [8][12] - Progress in the STAT6 program includes completing IND-enabling studies for KT-621 and initiating a Phase I healthy volunteer study [9][10] - The TYK2 program is advancing with the development candidate KT-295, with plans to start a Phase I healthy volunteer study [11][30] Market Data and Key Metrics Changes - The company aims to develop therapies that provide biologic-like efficacy with the convenience of an oral daily pill, targeting a broad patient population [8][16] - The strategic focus on immunology is expected to expand access to millions of patients globally [8] Company Strategy and Development Direction - Kymera is committed to developing an industry-leading immunology pipeline featuring innovative oral small molecule therapies [16] - The goal is to deliver at least one new IND per year, with multiple clinical advancements expected in 2025 [15][34] - The company plans to unveil a new immunology target in May, which aligns with its pipeline strategy [34] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress made in 2024 and the potential for a productive 2025 with several clinical advancements [12][34] - The company believes that its oral medicines can provide a differentiated solution compared to traditional small molecules and biologics [17] Other Important Information - The company is transitioning its quarterly financial updates to a video format to enhance transparency and communication with stakeholders [7] - A director, Leigh Morgan, will not stand for reelection at the upcoming Annual Shareholder Meeting [18] Q&A Session Summary Question: What supports your view that the 28 dosing in the atopic derm Phase Ib is enough time to show robust biomarker activity? - Management referenced prior dupilumab trials showing clear impacts on Th2 biomarkers at four weeks, indicating confidence in the 28-day study design [43][44] Question: Can you comment on the choice to not have a placebo arm in the Phase 1b? - Management believes that a placebo is unnecessary for demonstrating biomarker profiles, as biomarkers do not significantly change in placebo arms [49][50] Question: What do we know about the potential bioavailability of KT-621 in tissues of interest? - Preclinical data indicates that KT-621 is orally bioavailable and shows consistent degradation across various tissues, including skin and lungs [65][66] Question: How expansive of a Phase 3 development program would you expect to initiate for KT-621? - The company plans to run important Phase 2b studies to inform Phase 3 selection for potentially eight different indications, prioritizing asthma and atopic dermatitis [137][138]

Company and Industry Key Points **1. Tolebrutinib Phase 3 Data**: * **GEMINI 1 and 2 Trials**: Phase 3 trials evaluating Tolebrutinib in relapsing MS compared to Teriflunomide. No significant difference in annualized relapse rate, but a 29% risk reduction in confirmed disability worsening at six months with Tolebrutinib vs. Teriflunomide [7-13]. * **HERCULES Trial**: Phase 3 trial evaluating Tolebrutinib in non-relapsing secondary progressive MS. 31% risk reduction in time to six-month confirmed disability progression and 88% increase in six-month confirmed disability improvement vs. placebo [21-25]. * **Liver Safety**: 5.6% of Tolebrutinib-treated patients experienced liver enzyme elevation >3x upper limit of normal. All cases resolved without sequelae and occurred within the first 90 days of treatment [17-19, 27-28]. **2. Tolebrutinib's Mechanism of Action**: * Tolebrutinib appears to have a clear effect on reducing disability accumulation, independent of relapse rate or focal inflammatory disease. This suggests a potential for a new standard of care in SPMS [18, 20, 30]. **3. Frexalimab**: * Frexalimab, a CD40-Ligand inhibitor, is being investigated for MS. Phase 2 data shows promising results with low ARR and stable EDSS [36-37]. **4. Sanofi's Commitment to MS**: * Sanofi has a strong commitment to MS and is developing a comprehensive portfolio of treatments, including Tolebrutinib, Frexalimab, and other molecules [33-37]. Additional Important Points **1. Regulatory Approval**: * Sanofi plans to submit regulatory filings for Tolebrutinib in SPMS and is working on FDA labeling strategies [76-77]. **2. Patient Access**: * Sanofi aims to accelerate approval and make Tolebrutinib available to patients as soon as possible [32, 33]. **3. Future Research**: * Sanofi plans to conduct further research on Tolebrutinib and Frexalimab, including subgroup analyses and studies in other MS populations [95-97].

As filed with the Securities and Exchange Commission on December 18, 2023 Registration No. 333-275316 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 1 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 FIRST WAVE BIOPHARMA, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2834 46-4993860 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Identifica ...