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1.Bayer/Vincerx: BAY-943 BAY-943 (VIP943) is the first ADC (Antibody-Drug Conjugate) developed by Vincerx using the company's platform, consisting of an anti-CD123 antibody, a unique linker cleaved by legumain within the cell, and a novel payload of a kinesin spindle protein inhibitor (KSPi). A Phase 1 dose-escalation trial is currently underway to assess the treatment of patients with relapsed/refractory CD123 positive Acute Myeloid Leukemia (AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), or Myelodysplastic Syndromes (MDS) who are unresponsive to standard treatment regimens. The VNC-943-101 study is an open-label, multi-center, Phase 1 dose-escalation study using VIP943 as a monotherapy in patients with relapsed/refractory AML, B-ALL, and MDS. The primary objective of the trial is to determine the safe dosage of VIP943 for further clinical development. Three patients have been dosed in cohort 1 (0.2 mg/kg), and four patients in cohort 2 (0.4 mg/kg). All seven enrolled patients completed the 28-day DLT (Dose-Limiting Toxicity) assessment period. Pharmacokinetic (PK) data indicate that unbound free payload is minimal, consistent with the good safety profile observed preclinically and clinically. 2.AbbVie: Mirvetuximab Soravtansine Mirvetuximab soravtansine (also known as IMGN853, trade name: ELAHRET™) is the world's first antibody-drug conjugate (ADC) for folate receptor alpha (FRα)-positive ovarian cancer, developed by ImmunoGen, which was acquired by AbbVie. The drug was granted accelerated approval by the FDA in 2022; Huadong Medicine has the exclusive rights to it in Mainland China, Hong Kong, Macau, and Taiwan. The data disclosed herein pertain to a Phase II trial of mirvetuximab soravtansine (IMGN853) in combination with pembrolizumab for the treatment of patients with microsatellite-stable (MSS) recurrent or persistent endometrial cancer. Previously, the drug demonstrated good tolerability and single-agent activity in a Phase I dose-expansion study in patients with FRα-positive advanced/late-stage disease. The co-primary endpoints of the current study are objective response rate (ORR) measured according to RECIST 1.1 and the frequency of progression-free survival at 6 months (PFS6). Sixteen patients were enrolled in the first phase of the study; if ≥2 objective responses or ≥2 PFS6 responses were observed, an additional 19 patients would be recruited for the second phase. If a total of 4 objective responses or 8 PFS6 events were achieved, the combination would be considered worthy of further investigation. Results show that as of November 2023, a total of 16 patients had received study treatment, with a median follow-up of 4.7 months (IQR 2.9, 17.3). Among the 16 treated patients, 6 patients (37.5%, 95% CI: 15.2-64.6%) achieved an objective response, including 1 confirmed complete response (CR) and 5 partial responses (PR), with 3 confirmed PRs (18.8%) and 2 unconfirmed PRs (12.5%). Additionally, 31.3% (5/16) of patients had stable disease, with two patients surviving without progression at 6 months. In terms of safety, the most common treatment-related adverse events (TRAEs) included increased AST (50%), blurred vision (44%), fatigue (44%), and diarrhea (43%); two patients (12.5%) experienced a Grade 3 TRAE. Eye toxicity of any grade was reported in 56.3% of patients. 3.Novartis: JBH492 JBH492 is an ADC (Antibody-Drug Conjugate) that targets the CC-Chemokine Receptor 7 (CCR7). It is composed of a humanized anti-CCR7 IgG1 antibody conjugated to the maytansinoid microtubule inhibitor DM4 via a cleavable linker at a specific site. Preclinical studies have shown that this drug possesses effective target-dependent cytotoxic activity, demonstrating potent and durable efficacy in various clinically relevant lymphoma models. This disclosed study represents an ongoing first-in-human, open-label, phase I/Ib, multi-center trial being conducted in patients with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), which has completed enrollment for the dose-escalation phase. The purpose of dose escalation is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary efficacy of JBH492 and to determine the maximum tolerated dose (MTD) and the recommended dose. The study indicates that four NHL patients (two with T-cell NHL and two with B-cell NHL) experienced partial remission (PR), and two patients had stable disease, with PR observed at dosages ranging from 2.4 to 3.6 mg/kg every three weeks. Following the data cutoff, one patient with T-cell NHL achieved complete remission (CR) after four treatment cycles. No correlation between CCR7 expression and response could be established (CCR7 expression was observed in all samples from 14 patients). Regarding safety, 23 patients (92%) experienced at least one adverse event (AE) (Grade ≥ 3, n = 11). Fifteen patients (60%) reported treatment-related AEs (TRAEs) (Grade ≥ 3, n = 3). Of the six patients (24%) who had serious AEs (SAEs) (Grade ≥ 3, n = 3), two (8%) had TRSAEs. The most common AEs (≥ 20%) included anemia (32%), thrombocytopenia (28%), neutropenia, and dry eye syndrome (each 20%). There were two deaths due to underlying diseases. 4.ADC Therapeutics: Mipasetamab Uzoptirine Mipasetamab uzoptirine (ADCT-601) is a targeted Axl Antibody-Drug Conjugate (ADC) that consists of a humanized anti-AXL antibody conjugated to the pyrrolobenzodiazepine (PBD) dimer SG3199 via a cleavable linker. AXL is a cell surface receptor tyrosine kinase that is widely expressed in solid tumors (ST), including sarcomas. ADCT-601 has demonstrated antitumor activity in preclinical mouse models of sarcoma, adrenocortical carcinoma, and pancreatic cancer, and has shown clinical activity in ST patients during its first-in-human trials. In a Phase 1b, open-label, dose-escalation and dose-expansion study, patients were treated with ADCT-601 in a 3+3 dose-escalation design every three weeks at increasing dose levels. As of December 4, 2023, among 17 evaluable sarcoma patients according to RECISTv1.1, the best overall response was partial response (PR) (2 patients [11.8%]), including confirmed PR; stable disease (SD) (8 patients [47.1%]); and progressive disease (PD) (7 patients [41.2%]). Tumor reduction was observed at the doses of 7.5mg, 11mg, and 13mg. By week 12, 6/17 patients (35.3%) had not exhibited progression of disease (PD). In terms of safety, the most common treatment-emergent adverse events (TEAEs) of all grades and relationships (≥20%) were hand-foot syndrome (7 patients [38.9%]); anemia (6 patients [33.3%]); maculopapular rash (5 patients [27.8%]); cheilitis and constipation (4 patients each [22.2%]). TEAEs of grade ≥3 occurred in 9 patients (50%). The most common grade ≥3 TEAEs (≥10%) were increased GGT (2 patients [11.1%]). Two dose-limiting toxicities were observed: grade 2 and grade 3 cheilitis at doses of 15mg and 13mg, respectively. Skin reactions of all grades were more pronounced at higher doses. The maximum tolerated dose (MTD) has not yet been determined. 5.Roche: Trastuzumab Emtansine Trastuzumab emtansine is a HER2-targeted ADC that has been approved for the treatment of metastatic breast cancer with HER2 overexpression. HER2 point mutations are present in approximately 1.4% of solid tumors, but the prevalence varies among different tumor types. The TAPISTRY study disclosed here is a Phase II, global, open-label, multi-cohort trial designed to assess the efficacy and safety of several therapies in patients with advanced/metastatic solid tumors. The primary endpoint is the Objective Response Rate (ORR) as assessed by an Independent Review Committee (IRC), with key secondary endpoints including the ORR assessed by the researchers; duration of response; progression-free survival; overall survival rate; and drug safety. As of July 16, 2023, 35 patients with 10 different tumor types were evaluable for efficacy, with Non-Small Cell Lung Cancer (NSCLC) being the most common. After a median follow-up of 7 months, the ORR assessed by IRC for patients evaluable for efficacy was 14.3%; responses were observed in three tumor types: NSCLC (n/N=1/11), breast cancer (n/N=3/5), and endometrial carcinoma (n/N=1/1). The most common adverse events were decreased appetite, fatigue, and nausea (25.7% each). No new safety signals were found. 6.Heidelberg: HDP-101 HDP-101 is a BCMA-targeted ADC (antibody-drug conjugate) developed by Heidelberg, consisting of a BCMA antibody, VA-PABC linker, and an Amanitin derivative HDP 30.2115. Due to its high toxicity, the drug-to-antibody ratio (DAR) is set at 2, and a site-specific conjugation method is used to ensure homogeneity and reduce potential toxicity. As an immunoactivating agent, HDP-101 can induce immunogenic cell death (ICD) and shows synergistic effects with immune checkpoint inhibitors, offering possibilities for combination therapy in a clinical setting. The data disclosed here pertains to a first-in-human, open-label, non-randomized, multi-center, phase 1/2a trial aimed at determining the maximum tolerated dose and establishing a phase 2 trial recommended dose in patients with multiple myeloma. As of November 2023, 18 patients (7 females and 11 males) have been enrolled across 5 sequential dose cohorts with doses of 20, 30, 60, 80, and 100 µg/kg. Preliminary data indicates that the pharmacokinetics of HDP-101 are in line with expectations, and the exposure to HDP-101 is dose-proportional. Patients in cohort 3 exhibited stable disease (SD) after 15 cycles. In cohort 5, there are 4 ongoing patients who have shown promising results after 3-4 cycles: 2 patients achieved partial response (PR), and 2 patients reached SD. In terms of safety, the drug was well tolerated with no dose-limiting toxicities (DLT), including no signs of hepatorenal toxicity, infusion reactions, or ocular diseases. Of the 18 patients across the 5 treatment groups, 17 were evaluable for DLT assessment. 7.Daiichi Sankyo/AstraZeneca: Trastuzumab Deruxtecan Trastuzumab deruxtecan (T-DXd), also known as fam-trastuzumab deruxtecan-nxki, is an antibody-drug conjugate (ADC) that targets HER2, composed of a humanized anti-HER2 antibody, an enzymatically cleavable peptide linker, and a topoisomerase I inhibitor. The disclosed phase 2 DESTINY-Lung05 (DL-05) trial was conducted to evaluate its efficacy in Chinese patients with previously treated HER2-mutant non-small cell lung cancer (NSCLC). This open-label, single-arm, phase 2 trial primarily aimed to assess the objective response rate (ORR) confirmed by an Independent Central Review (ICR); secondary endpoints included ORR confirmed by investigator's assessment (INV), duration of response, disease control rate, progression-free survival, and safety evaluated by both ICR and INV. The results, as of September 23, 2023, demonstrated that the median exposure to T-DXd was 7.9 (0.7-13.5) months. A total of 71 patients experienced drug-related adverse events (AEs), with 51.4% being grade (G) ≥3. The most common G≥3 AEs by grouped terms included neutropenia (26.4%), thrombocytopenia (18.1%), and leukopenia (11.1%). Two patients (2.8%) experienced drug-related AEs leading to discontinuation of treatment. Seventeen patients (23.6%) experienced serious AEs with no G5 determined by INV. Central adjudication identified drug-related interstitial lung disease (ILD)/pneumonitis in 7 patients (9.7%; n=6 G2; n=1 G5). This suggests that the safety profile in the Chinese patient population is consistent with the known safety data.

PALO ALTO, Calif., Sept. 14, 2023 (GLOBE NEWSWIRE) -- Vincerx Pharma Inc. (Nasdaq: VINC)(“Vincerx”), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, today reported that the first patient has been dosed in the Phase 1 trial evaluating VIP943 in patients with relapsed/refractory acute myeloid leukemia (R/R AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-cell ALL), NCT06034275. "Dosing of the first patient is a major achievement for the VIP943 development program and our next-generation bioconjugation platform. This achievement occurred 17 business days from receiving our safe to proceed letter, underscoring the enthusiasm from our investigators and the strong execution capabilities of the Vincerx team," said Ahmed Hamdy, M.D., Chief Executive Officer of Vincerx. "VIP943 is the first ADC candidate from our pioneering bioconjugation platform, designed to address the challenges of current ADCs, by increasing the therapeutic index (ie, increasing efficacy and reducing toxicity). We are the first company to bring to the clinic a legumain-cleavable linker and the first to utilize a kinesin spindle protein inhibitor (KSPi) as an ADC payload. This innovative and proprietary combination has generated strong preclinical evidence of activity and safety and has the potential to shift the treatment paradigm for patients with CD123+ hematologic malignancies. We look forward to evaluating the potential of VIP943 and expect to report preliminary safety and pharmacology data from our Phase 1 study in 2024." Stephen A. Strickland, Jr., M.D., MSCI, Director of Leukemia Research for the Sarah Cannon Research Institute (SCRI) and Principal Investigator on the Phase 1 trial for VIP943, said, “Despite there being new medicines for hematologic malignancies such as AML, MDS and B-cell ALL, outcomes for many patients have not improved and relapse rates remain high. The urgent need for more effective treatment options persists. Several factors influence the outlook for these cancers including increased frequency in older patients and poor response rates, especially in patients who relapse after initial therapy. Vincerx’s preclinical data provides a strong rationale to support the evaluation of VIP943 in the setting of hematologic malignancies, with hopes of providing more effective and less toxic therapeutic options for patients.” Howard A. “Skip” Burris, III, M.D., President of SCRI and Scientific Advisory Board member for Vincerx, said, “There is growing hope for delivering targeted therapies through the use of ADCs. Targeting hematologic malignancies with an ADC that combines selective binding to CD123 and a potentially improved safety profile, compared to other ADCs and CD123-targeting therapies, could provide a much needed treatment option for patients. Our team is excited to collaborate with Vincerx and begin enrolling patients in this Phase 1 dose escalation study.” About VIP943 VIP943 is the lead program from our next-generation ADC platform. VIP943 binds to CD123, a validated target in myeloid malignancies. Once inside the cell, it is only cleaved by an intracellular protein called legumain, allowing specific release and activation of the KSPi payload within the cancer cell. KSPi provides a novel way to deliver a cell cycle arrest agent, leading to cell death, which is a clinically validated ADC payload class mechanism. Vincerx’s novel legumain-specific linker substantially reduces non-specific release of the payload, thereby reducing unwanted side effects on healthy cells. In addition, Vincerx’s CellTrapper™ technology ensures that the KSPi payload accumulates in the target cells, limiting uptake into non-target, non-dividing cells. The innovative and intentional combination of a validated CD123 antibody, an intracellular cleavable legumain linker, and a potent KSPi payload holds the potential to address prevalent challenges of many ADCs by increasing the therapeutic window, thus improving efficacy and reducing common, severe toxicities such as myelosuppression, infections, peripheral neuropathy, and hepatotoxicity. VIP943 has demonstrated increased survival and reduced tumor burden in AML cell lines and patient-derived tumor models. Additionally, Vincerx presented preclinical data on VIP943 at ASH 2022, demonstrating superiority versus Mylotarg™, an approved ADC, with significantly improved safety in monkeys and better efficacy in a mouse model of acute leukemia. Preclinical data suggest that VIP943 does not induce significant cytokine release syndrome, common to other CD123-targeting agents, and demonstrated favorable safety in monkeys, with an optimal drug metabolism and pharmacokinetics profile. The Phase 1 trial of VIP943 is intended to assess safety, pharmacokinetics/pharmacodynamics, and preliminary efficacy of VIP943 in patients with R/R AML, MDS and B-cell ALL. The study will be conducted in several prominent U.S. cancer centers. About Vincerx Pharma, Inc. Vincerx Pharma, Inc. is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. The company’s diverse pipeline consists of the next-generation antibody conjugate, VIP943, in Phase 1; small molecule drug-conjugate, VIP236, in Phase 1; preclinical antibody drug conjugate, VIP924; CDK9 inhibitor, enitociclib, currently in an NIH-sponsored Phase 1; and its next-generation modular bioconjugation platform. Vincerx is based in Palo Alto, California, and has a research facility in Monheim, Germany. For more information, please visit . Forward-Looking Statement This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended, that are intended to be covered by the “safe harbor” created by those sections. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, expectations and events, can generally be identified by the use of forward-looking terms such as “believe,” “expect,” “may,” “will,” “should,” “would,” “could,” “suggest,” “seek,” “intend,” “plan,” “goal,” “potential,” “on-target,” “on track,” “project,” “estimate,” “anticipate,” or other comparable terms. All statements other than statements of historical facts included in this press release are forward-looking statements. Forward-looking statements include, but are not limited to: Vincerx’s business model, pipeline, strategy, timeline, product candidates and attributes, and preclinical and clinical development, timing, and results. Forward-looking statements are neither historical facts nor assurances of future performance or events. Instead, they are based only on current beliefs, expectations, and assumptions regarding future business developments, future plans and strategies, projections, anticipated events and trends, the economy, and other future conditions. Forward-looking statements are subject to inherent uncertainties, risks, and changes in circumstances that are difficult to predict and many of which are outside of Vincerx’s control. Actual results, conditions, and events may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause actual results, conditions, and events to differ materially from those indicated in the forward-looking statements include, but are not limited to: general economic, financial, legal, political, and business conditions; the potential effects of health epidemics and pandemics, including COVID-19; risks associated with preclinical or clinical development and trials, including those conducted prior to Vincerx’s in-licensing; failure to realize the benefits of Vincerx’s license agreement with Bayer; risks related to the rollout of Vincerx’s business and the timing of expected business and product development milestones; changes in the assumptions underlying Vincerx’s expectations regarding its future business or business model; Vincerx’s ability to successfully develop and commercialize product candidates; Vincerx’s capital requirements and availability and uses of capital; and the risks and uncertainties set forth in Form 10-Q for the quarter ended June 30, 2023 and other reports filed with the Securities and Exchange Commission by Vincerx. Forward-looking statements speak only as of the date hereof, and Vincerx disclaims any obligation to update any forward-looking statements. Vincerx and the Vincerx logo are our trademarks. This press release also contains trademarks and trade names that are the property of their respective owners. Contacts Gabriela Jairala Vincerx Pharma, Inc. gabriela.jairala@vincerx.com Joyce Lonergan LifeSci Advisors, LLC 781-528-5276 JLonergan@lifesciadvisors.com

VIP924, a first-in-class CXCR5-ADC showed significant activity in patient-derived (PDX) lymphoma mouse models PALO ALTO, CA, USA I April 19, 2023 I Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, today presented a poster of VIP924 preclinical data at the 2023 American Association for Cancer Research (AACR) Annual Meeting. VIP924 consists of an anti-CXCR5 humanized monoclonal antibody with a novel linker containing a unique peptide sequence specifically cleaved by legumain—a tumor-associated lysosomal protease. Inside the tumor cell, upon legumain cleavage, the active payload, VIP716, is released. VIP716 is a novel highly potent and selective kinesin spindle protein inhibitor (KSPi), which has been modified with a hydrophilic CellTrapper™ moiety to reduce membrane permeability without having a negative impact on efficient target binding. This modification allows for intracellular accumulation of VIP716 in CXCR5+ tumor cells, providing greater efficacy, and prevents cellular penetration into healthy tissues, reducing toxicity. “We are thrilled to continue advancing our bioconjugation platform with our newest ADC, VIP924,” said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx. “At AACR, VIP924 showed meaningful preclinical activity in a panel of lymphoma cell lines and in cell line-derived and patient-derived lymphoma mouse models. Most notably, mouse models implanted with tumor cells from lymphoma patients demonstrated significant tumor growth inhibition and prolonged survival after VIP924 treatment. Showing activity in mouse models implanted with tumor cells from patients, also known as PDX models, is particularly meaningful because PDX models are more representative of the complexity of human cancer than results seen with cell lines.” Dr. Hamdy continued, “Despite progress in the treatment of B-cell malignancies, there is still an unmet medical need, especially for patients with relapsed or refractory disease. The results presented at AACR, together with our previous efficacy findings of durable complete tumor regression in CXCR5-positive, ibrutinib-refractory lymphoma models, suggest that VIP924 has the potential to be a treatment option for relapsed and refractory patients. Looking at the totality of preclinical data we’ve generated, including the data we presented at ASH that showed how our next generation linker, payload, and CellTrapper™ technology significantly improved the safety and efficacy of the approved ADC, Mylotarg™, we can’t help but be excited about the future of our ADC programs. We look forward to filing the IND for VIP924 in mid-2024.” Key Presentation Highlights: Poster presentation, titled, CXCR5 is a very promising drug target for the development of antibody-drug conjugates to treat patients with lymphoma , presented by Tibor Schomber, Ph.D., Vincerx Pharma GmbH, Monheim, Germany, include: The poster can be accessed on the presentations section of the Vincerx website. About Vincerx Pharma, Inc. Vincerx Pharma, Inc. (Vincerx) is a clinical-stage biopharmaceutical company committed to developing differentiated and novel therapies to address the unmet medical needs of patients with cancer. Vincerx has assembled a seasoned management team with a proven track record of successful oncology drug development, approvals, and value creation. The company’s diverse pipeline consists of enitociclib, currently in Phase 1, and a proprietary modular bioconjugation platform, which includes a small molecule drug-conjugate, VIP236, in Phase 1, and preclinical next-generation antibody drug conjugates, VIP943 and VIP924. Vincerx is based in Palo Alto, Calif., and has a research facility in Monheim, Germany. For more information, please visit www.vincerx.com . SOURCE: Vincerx Pharma