Daraxonrasib

编者按 2025年度肿瘤领域涌现了哪些具有里程碑意义的研究？哪些突破正在重塑临床实践？【医悦汇】年度盘点栏目力邀国内多位顶尖专家，拨开迷雾，聚焦精髓，对全年最重磅的进展进行权威梳理与深度解读。本系列盘点旨在为同道呈献一份脉络清晰、见解独到的年度学术答卷，共同前瞻未来方向。 本期盘点由北京协和医院巴一教授、王晰程教授、汤加博士共同撰稿，系统梳理2025年度结直肠癌靶向治疗领域的重要临床研究进展，并对未来发展趋势进行展望，以馈读者！ 结直肠癌靶向治疗领域在2025年取得了显著进展，主要体现在新型药物研发和临床治疗策略的优化。针对特定分子亚型，如BRAF突变、HER2扩增、RAS突变等的精准治疗取得重要突破，双特异性抗体及抗体药物偶联药物在晚期患者中展现出良好的应用前景。随着多项关键临床研究数据的公布，结直肠癌靶向治疗正朝着更加精准化和联合治疗的方向发展。而新的治疗策略不仅提高了治疗效果，还改善了患者的生存质量。 BRAF抑制剂 BRAF是MAPK通路中的重要组成部分，其突变发生在约8%-12%的转移性结直肠癌患者中，以BRAF V600E突变为主。此前，Ⅲ期BEACON研究证实了BRAF抑制剂康奈非尼（encorafenib）联合西妥昔单抗在BRAF V600E突变型CRC后线治疗中的有效性。2025年，ASCO年会报告了Ⅲ期BREAKWATER研究的结果：康奈非尼联合西妥昔单抗与FOLFOX方案化疗和标准治疗相比，在BRAF V600E突变型转移性结直肠癌一线治疗的ORR分别为60.9%和40%，PFS（12.8 vs. 7.1个月）和OS（30.3 vs. 15.1个月）均显著延长。BREAKWATER研究将BRAF抑制剂和EGFR抑制剂联合从后线治疗成功前移至一线治疗，实现了该难治亚型治疗的历史性突破。 HER2靶向药物 结直肠癌中，HER2扩增/过表达的发生率约为3%-4%。抗HER2治疗的有效性在乳腺癌、胃癌等瘤种的治疗中已得到充分验证，其在结直肠癌中的应用也逐渐受到关注。2025年ESMO会议报告了DESTINY-CRC02 Ⅱ期研究的最终分析：和初步分析一致，德曲妥珠单抗（Trastuzumab Deruxtecan）用于HER2阳性经治的mCRC患者在5.4mg/kg剂量组的cORR和中位PFS均优于6.4mg/kg剂量组；且5.4mg/kg剂量组药物相关的3级及以上不良事件发生率（42.2%）低于6.4mg/kg剂量组（48.7%），间质性肺炎的发生率分别是9.6%和17.9%。虽然5.4mg/kg剂量组的中位OS（15.9个月，95%CI：12.6-18.8个月）低于6.4mg/kg剂量组（19.7个月，95%CI：9.9-25.8个月），但后者的OS置信区间较宽，且不良反应发生率较高。因此，仍支持5.4mg/kg剂量为安全且有效的临床剂量。目前，DESTINY-PanTumor03（NCT06271837）研究正在国内开展，将纳入包括结直肠癌在内的多个瘤种，并采用5.4mg/kg剂量，期待其研究数据的公布。 近年来，HER2双特异性靶向药物正得到积极开发。泽尼达妥单抗（zanidatamab）是一种HER2双特异性抗体，可同时靶向HER2受体的ECD4和ECD2结构域。2025年ESMO会议报道了一项泽尼达妥单抗+FOLFOX化疗±贝伐珠单抗一线治疗HER2阳性mCRC的Ⅱ期研究（NCT03929666）的2年随访结果：共纳入13例患者，在11例疗效可评估的患者中，cORR为100%，所有患者均达到PR；总体中位PFS尚未达到。此外，HER2双特异性ADC，如JSKN003，TQB2102等药物也正在临床开发阶段。2025年ESMO会议报道了JSKN003-102研究（NCT05744427）的结果：33例经标准治疗失败的HER2阳性mCRC患者接受JSKN003单药治疗，ORR达66.7%，初步中位PFS为11.04个月。近期JSKN003也获得了NMPA用于治疗HER2阳性晚期结直肠癌的突破性治疗认定。 RAS抑制剂 2025年RAS抑制剂领域取得重要突破，临床研究数据进一步验证了其治疗潜力。索托拉西布（Sotorasib）联合帕尼单抗的方案在KRAS G12C突变晚期结直肠癌患者中显示出显著疗效。根据最新公布的Ⅲ期CodeBreaK 300随机对照试验数据，索托拉西布960mg剂量联合帕尼单抗在53例患者中达到30.2%的客观缓解率，疾病控制率为71.7%，中位无进展生存期为5.7个月。相比之下，240mg剂量组的疗效相对较低，客观缓解率仅为7.5%，提示剂量选择对治疗效果具有重要影响。 针对KRAS G12D突变的研究也在开展中，目前已有十余种候选药物进入临床开发阶段。Zoldonrasib（RMC-9805）作为RAS ON状态抑制剂，已进入Ⅰ/Ⅱ期临床试验（NCT06162221）。Pan-RAS抑制剂能够同时抑制KRAS，HRAS和NRAS等多种RAS亚型。Daraxonrasib（RMC-6236）在胰腺癌中已取得良好表现，期待其在结直肠癌等其它实体瘤中的应用开发。目前，另有数款针对实体瘤的Pan-RAS抑制剂正在临床I期研究阶段。 此外，多项关键Ⅲ期研究正在进行中，旨在进一步验证RAS抑制剂在结直肠癌中的临床价值。KRYSTAL-10研究（NCT04793958）比较Adagrasib（KRAS G12C抑制剂）联合西妥昔单抗与标准化疗在二线治疗中的疗效，预计2026年1月完成主要终点评估。CodeBreaK 301研究（NCT06252649）探索索托拉西布在一线和化疗联合治疗的应用，预计2028年1月获得PFS数据。这些研究结果的公布预计将对RAS抑制剂的临床应用产生重要影响。 c-MET抑制剂 及其他新兴靶向治疗进展 c-MET抑制剂 c-MET信号通路激活与结直肠癌的进展、转移及不良预后密切相关，其靶向治疗在2025年展现出重要潜力。双特异性抗体Amivantamab通过同时靶向EGFR和c-MET，在晚期结直肠癌中显示出良好疗效。根据OrigAMI-1试验数据，该药物联合化疗方案在一线治疗患者中缓解率达到64%，中位无进展生存期为7.5个月，整体安全性可控。目前，其对比西妥昔单抗一线治疗转移性结直肠癌的Ⅲ期研究OrigAMI-2正在进行中。 抗体药物偶联物ABBV-400（telisotuzumab adizutecan）在c-MET高表达晚期结直肠癌患者中表现出单药及联合治疗活性。研究数据显示，该药物联合贝伐珠单抗在63例患者中，中位PFS达6.7个月，中位OS达13.8个月，显著优于对照组，支持其作为c-MET高表达患者的重要治疗选择。相关Ⅲ期研究（NCT05029882）也已开展。此外，c-MET抑制剂与MEK抑制剂的联合策略（如克唑替尼联合PD-0325901）在24例晚期实体瘤患者中显示出29%的疾病控制率，耐受性良好。 双特异性抗体与ADC药物 双特异性抗体及抗体药物偶联物（ADC）在结直肠癌治疗中呈现多元化发展。除前述c-MET/EGFR双特异性抗体外，多种创新双特异性抗体进入临床研究阶段，如PD-1/VEGF双特异性抗体依沃西单抗、PD-1/CTLA-4双特异性抗体卡度尼利单抗（NCT06566755）、CEA/CD3双特异性抗体Cibisatamab（NCT02324257，NCT02650713）、B7-H3/CD3双特异性抗体CC-3（NCT05999396）等，丰富了治疗选择。 ADC药物方面，针对CEACAM5的Precemtabart tocentecan在2025年ESMO会议报告的Ⅰ期研究中显示出积极数据：在60例经治晚期结直肠癌患者中，2.8mg/kg剂量组确认的ORR为17.2%，DCR达72.4%，主要不良反应为可控的血液学毒性。此外，针对PD-L1，B7-H3等靶点的ADC药物（如HLX43，HS-20093等）也处于不同研发阶段，为特定生物标志物阳性患者提供了新的治疗机会。 其他新兴靶点 Polo样激酶1（PLK1）在约70%的结直肠癌中过表达，其表达水平与患者预后负相关。研究显示，PLK1抑制剂Onvansertib联合FOLFIRI方案及贝伐珠单抗，用于KRAS突变型转移性结直肠癌二线治疗，客观缓解率达26.4%，展现出独特治疗价值。 钙黏蛋白17（CDH17）作为消化系统肿瘤的重要标志物，其高水平表达与不良预后相关，已成为具有成药前景的新靶点。目前全球有十余种CDH17靶向药物处于临床研究阶段，其中国产ADC药物占据重要地位，虽尚未有结果公布，但有望成为使患者获益的新治疗靶点。 总结与展望 2025年，结直肠癌靶向治疗在精准化与多元化方面取得显著进步，多个关键靶点领域均实现重要突破。BRAF抑制剂联合方案凭借BREAKWATER研究成功实现治疗前移，为BRAF V600E突变患者一线治疗带来历史性改善。HER2靶向治疗领域，德曲妥珠单抗最佳剂量得以明确，泽尼达妥单抗及JSKN003等新型双特异性抗体/ADC药物展现出卓越疗效，为HER2阳性患者提供了多样化选择。RAS抑制剂研究取得关键进展，索托拉西布等药物在KRAS G12C突变患者中证实疗效，并向更广谱突变亚型及一线治疗拓展。c-MET靶向治疗中，双特异性抗体及ADC药物为特定生物标志物阳性患者带来新的希望。此外，针对CEACAM5，PLK1，CDH17等新兴靶点的药物研发也呈现出活跃态势，进一步丰富了治疗格局。 展望未来，本领域发展将聚焦于几个关键方向：一是深入探索耐药机制，开发新一代靶向药物以克服耐药问题；二是推动高效治疗方案前移，持续优化一线治疗策略；三是完善生物标志物检测体系，实现更精细的患者分层与个体化治疗；四是探索不同作用机制药物的联合策略，最大化临床获益。 随着创新药物的研发及临床数据的积累，结直肠癌的个体化治疗水平将进一步提升，为患者带来长期生存希望。 参考文献： 1. Elez E, Yoshino T, Shen L, et al. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N Engl J Med. 2025;392(24):2425-2437. 2. Raghav K, Siena S, Takashima A, et al. 737MO Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic colorectal cancer (mCRC): Final analysis of DESTINY-CRC02, a randomized, phase II trial[J]. Annals of Oncology, 2025, 36: S514-S515. 3. Rha S Y, Lee K W, Lee S, et al. 746P A 2-year follow-up of zanidatamab (Zani)+ mFOLFOX6±bevacizumab (Bev) in first-line (1L) treatment of patients (Pts) with human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC)[J]. Annals of Oncology, 2025, 36: S521-S522. 4. Liu D, Liu B, Zhang X, et al. 806P Efficacy and safety of JSKN003: A biparatopic anti-HER2 antibody conjugate (ADC), in patients with HER2-positive metastatic colorectal cancer (mCRC)[J]. Annals of Oncology, 2025, 36: S548. 5. Pietrantonio F, Salvatore L, Esaki T, et al. Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer. J Clin Oncol. 2025;43(19):2147-2154. 6. Pietrantonio F, Ho G F, Su Y L, et al. 513MO Amivantamab plus FOLFOX or FOLFIRI in metastatic colorectal cancer: Results from OrigAMI-1, an open-label, phase Ib/II study[J]. Annals of Oncology, 2024, 35: S434. 7. Arnold D, Cervantes A, Ducreux M P, et al. OrigAMI-2: A randomized, phase 3 study of amivantamab vs cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line treatment in left-sided RAS/BRAF wild-type metastatic colorectal cancer[J]. 2025. 8. Cecchini M, Cruz-Correa M, Han S W, et al. 731MO Telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Dose expansion results of a phase I study[J]. Annals of Oncology, 2025, 36: S511-S512. 9. Strickler J H, Kawazoe A, Li J, et al. Telisotuzumab adizutecan (ABBV-400; Temab-A) monotherapy vs trifluridine/tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer with increased c-Met protein expression: An open-label, randomized, phase 3 trial[J]. 2025. 10. Gallagher P, Rolfo C, Elez E, et al. A phase Ia study of the MEK1/2 inhibitor PD-0325901 with the c-MET inhibitor crizotinib in patients with advanced solid cancers[J]. BJC reports, 2025, 3(1): 17. 11. Shoji H, Han S W, Andreas M, et al. 1O Precemtabart tocentecan (M9140): Initial results from the phase I PROCEADE-CRC-01 dose optimization study and preclinical antitumor activity across tumor models[J]. ESMO Open, 2025, 10. 12. Ahn D H, Ridinger M, Cannon T L, et al. Onvansertib in combination with chemotherapy and bevacizumab in second-line treatment of KRAS-mutant metastatic colorectal cancer: A single-arm, phase II trial[J]. Journal of Clinical Oncology, 2025, 43(7): 840-851. 13. Ye P, Zhang Z, Zhang D, et al. PLK1 inhibitors for the treatment of colorectal cancer[J]. Annals of Medicine and Surgery, 2025, 87(7): 4165-4172. 14. Ng L, Yu WS, Aung NM, et al. Tissue Cadherin 17 (CDH17): An Important Prognostic Determinant of Colorectal Cancer Using Digital Image Analysis. Cancer Rep (Hoboken). 2024;7(12):e70069. 指导专家 巴一 教授、主任医师、博士生导师 北京协和医院肿瘤医学中心主任、肿瘤内科主任 ▶ 教育部“新世纪人才”、人社部“国家百千万人才”，享受国务院特殊津贴 ▶ 中国医学科学院北京协和医学院长聘教授 ▶ 中国药学会抗肿瘤药物专业委员会主任委员 ▶ CSCO临床研究专家委员会副主任委员 ▶ 国家卫健委结直肠癌指南专家 ▶ 中国抗癌协会罕见突变及罕见肿瘤专业委员会主任委员 ▶ 中国抗癌协会肿瘤支持专业委员会第一任主任委员 ▶ 中国医师协会肿瘤分会前副会长 审校专家 王晰程 主任医师 北京协和医院肿瘤医学中心副主任 ▶ 中国抗癌协会罕见突变及罕见肿瘤专委会常委 ▶ 中国抗癌协会遗传性肿瘤专委会常委 ▶ 中国抗癌协会大肠癌专委会委员 ▶ CSCO结直肠癌专委会委员 ▶ 北京癌症防治学会直肠癌新辅助治疗专委会副主委 盘点专家 汤加 主治医师 北京协和医院肿瘤医学中心 ▶ 北京协和医学院临床医学（八年制）博士 ▶ 北京协和医院肿瘤学博士后 免责声明：本账号分享的内容仅为健康信息科普，不构成任何医疗建议。个人健康问题，请务必咨询执业医师。 编辑 | 晓娟 排版 | Luna 审核 | 佼娇 鹏哥 王晰程 版权声明： 本文版权归医悦汇所有，欢迎转发分享！ 其他任何媒体如需转载或引用本网版权所有内容，须获得授权，且在醒目位置处注明 “ 转自：医悦汇 ”。

Encouraging early clinical activity, including confirmed partial responses in multiple tumor types with different RAS mutations, coupled with promising safety and pharmacokinetics data, observed for ERAS-0015 during dose escalation Initial Phase 1 monotherapy data for ERAS-0015 (potential best-in-class pan-RAS molecular glue) planned for H1 2026 and for ERAS-4001 (potential first-in-class pan-KRAS inhibitor) planned for H2 2026 SAN DIEGO, Jan. 12, 2026 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced meaningful clinical progress for its RAS-targeting franchise and 2026-2027 milestones. “With both ERAS-0015 and ERAS-4001 INDs previously cleared in May 2025, Erasca’s strong operational execution continues to result in rapid clinical advancement of our RAS-targeting franchise. Notably, ERAS-0015 is now enrolling ahead of plan, thus providing early clinical data,” said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. “During dose escalation, ERAS-0015 has already demonstrated promising early clinical activity with multiple ongoing confirmed and unconfirmed responses achieved, along with encouraging safety and tolerability data and well-behaved PK. We believe that observing first clinical responses in multiple patients at just 1/10 th of the dose at which first clinical responses were observed with RMC-6236 is thesis-reinforcing in terms of ERAS-0015’s potential differentiation.” Pipeline Progress and 2026-2027 Milestones ERAS-0015 – Potential best-in-class RAS-targeting molecule Dose escalation in ongoing AURORAS-1 Phase 1 trial advancing faster than anticipated due to significant unmet medical need and high investigator and patient enthusiasm Ongoing confirmed and unconfirmed responses observed in multiple patients with differing tumor types and RAS mutations Ongoing responses (two confirmed partial responses (PRs) and one unconfirmed PR) observed in patients with different tumor types and RAS mutations achieved at a low dose of 8 mg QD Additional ongoing unconfirmed responses observed in patients at doses above 8 mg QD Favorable safety and tolerability, with no dose-limiting toxicities and predominantly low-grade adverse events observed at all dose levels evaluated to date* Well-behaved, linear pharmacokinetics (PK) across all dose levels evaluated to date with no evidence of exposure plateau* Milestones Initial Phase 1 monotherapy data in patients with RAS-mutant solid tumors planned for the first half of 2026** Initiation of monotherapy expansion cohorts and combination dose escalation cohorts planned for the second half of 2026 Monotherapy expansion data and combination dose escalation data planned for 2027** * Data cutoff date was January 7, 2026 ** Topline safety, tolerability, PK, and initial efficacy data ERAS-4001 – Potential first-in-class pan-KRAS inhibitor Dose escalation in ongoing BOREALIS-1 Phase 1 trial continues to advance as expected Milestones Initial Phase 1 monotherapy data in patients with KRAS-mutant solid tumors planned for the second half of 2026** Initiation of monotherapy expansion cohorts and combination dose escalation cohorts planned for 2027 ** Topline safety, tolerability, PK, and initial efficacy data About ERAS-0015 ERAS-0015 is an oral, highly potent pan-RAS molecular glue designed to inhibit RAS signaling with a potential best-in-class profile. Erasca is evaluating ERAS-0015 in the AURORAS-1 Phase 1 trial in patients with RAS-mutant solid tumors. Early dose escalation data in AURORAS-1 demonstrated favorable safety and tolerability, well-behaved, linear PK, and confirmed and unconfirmed responses in multiple patients across multiple tumor types with different RAS mutations, including confirmed and unconfirmed partial responses at doses as low as 8 mg once daily (QD). In preclinical studies versus RMC-6236, ERAS-0015 demonstrated approximately 8-21 times higher binding affinity to cyclophilin A (CypA) , approximately 5 times greater potency in RAS inhibition, and greater in vivo antitumor activity evidenced by achieving comparable or greater tumor growth inhibition or regression at doses that are as low as approximately one-tenth to one-fifth of the dose of RMC-6236. ERAS-0015 is also designed to prevent resistance against mutant-selective inhibitors through inhibition of RAS wildtype variants. In addition, ERAS-0015 has demonstrated favorable absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic (PK) properties in multiple animal species. About ERAS-4001 ERAS-4001 is an oral, highly potent, and selective pan-KRAS inhibitor with a potential first-in-class and best-in-class profile. Erasca is evaluating ERAS-4001 in the BOREALIS-1 Phase 1 trial in patients with KRAS-mutant solid tumors. ERAS-4001 demonstrated favorable preclinical in vitro potency against KRAS G12X mutations as well as KRAS wildtype amplifications, which may limit treatment resistance mediated through KRAS wildtype activation. No activity was observed for ERAS-4001 against HRAS or NRAS wildtype proteins in preclinical studies, which may enable a better therapeutic window compared to pan-RAS inhibitors. ERAS-4001 showed potent activity against both GTP-bound (active state) and GDP-bound (inactive state) KRAS with single digit nanomolar IC50s. In vivo, ERAS-4001 induced tumor regression in multiple KRAS-mutant models. In preclinical studies, ERAS-4001 showed encouraging ADME and PK properties. About Erasca At Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of patients with cancer. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer. Cautionary Note Regarding Forward-Looking Statements Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including ERAS-0015 and ERAS-4001, and the planned advancement of our development pipeline, including the anticipated timing of data readouts for the AURORAS-1 and BOREALIS-1 trials. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: preliminary results of a clinical trial are not necessarily indicative of final results and one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data and as more patient data becomes available, including the risk that an unconfirmed partial response to treatment may not ultimately result in a confirmed partial response to treatment after follow-up evaluations; observations regarding the first dosage level at which a clinical response is detected are based on data generated within individual clinical trials, and comparisons of such clinical observations across different trials involve data from separate trials with distinct designs, patient populations, and methodologies, and therefore may not be directly comparable; any forward-looking statements regarding dose-response relationships reflect current expectations and/or assumptions are subject to risks and uncertainties that could cause actual results to differ materially; our assumptions about the development potential of ERAS-0015 and ERAS-4001 are based in large part on the preclinical data generated by the licensors and we may observe materially and adversely different results as we conduct our planned studies and trials; our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; results from preclinical studies or early clinical trials not necessarily being predictive of future results; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, data readout, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; unfavorable results from preclinical studies or clinical trials; we may be unable to secure partnerships or other strategic collaborations for naporafenib on acceptable terms or at all; the inability to realize any benefits from our current licenses, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; regulatory developments in the United States and foreign countries; our ability to obtain and maintain intellectual property protection for our product candidates and maintain our rights under intellectual property licenses; the sufficiency of our cash, cash equivalents, and marketable securities to fund operations; we may use our capital resources sooner than we expect; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ended December 31, 2024, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com