Breast Cancer Prevention Partners

– Overall response rate of 42% and median progression-free survival of 11.1 months in heavily pre-treated patients (after 11 months median follow-up time and based on 48% of events) demonstrates the potential of vepdegestrant in combination with palbociclib (IBRANCE®) – – Tolerability generally consistent with the profile of palbociclib and what has been observed in other clinical trials of vepdegestrant– – Pending additional data and agreement with regulatory authorities, Arvinas and Pfizer plan to broaden development of vepdegestrant to include new combinations with CDK inhibitors in both the first- and second-line settings – NEW HAVEN, Conn. and NEW YORK, Dec. 05, 2023 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced clinical data for vepdegestrant (ARV-471), a novel oral PROteolysis TArgeting Chimera (PROTAC®) estrogen receptor (ER) degrader, in combination with palbociclib (IBRANCE®). Interim results from the Phase 1b combination cohort demonstrate encouraging clinical activity in heavily pre-treated patients with a median of four lines of therapy across disease settings with locally advanced or metastatic ER positive/human epidermal growth factor 2 (HER2) negative (ER+/HER2-) breast cancer. These data will be presented in a spotlight presentation at the 2023 San Antonio Breast Cancer Symposium (SABCS). “We are thrilled to see this level of clinical activity in such a heavily pre-treated patient population,” said John Houston, Ph.D., chairperson, chief executive officer, and president at Arvinas. “Vepdegestrant is the only PROTAC® ER degrader in late-stage clinical development. The results from this trial evaluating vepdegestrant in combination with palbociclib help advance our goals of benefitting patients with ER+/HER2- breast cancer. It is encouraging to see preliminary signals of activity in both wild-type and ESR1 mutant tumors, with manageable tolerability and low rates of discontinuation.” Vepdegestrant is a PROTAC® ER degrader designed to directly harness one of the cell’s natural protein disposal processes to specifically target and degrade the estrogen receptor. Vepdegestrant is being co-developed by Arvinas and Pfizer and is currently being evaluated as a monotherapy in the second-line setting in the ongoing Phase 3 VERITAC-2 trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase 3 VERITAC-3 trial. “Our goal is to develop a novel, tolerable next-generation estrogen-targeting agent that can help patients with ER+/HER2- breast cancer address disease progression,” said Adam Schayowitz, Ph.D., vice president, development head, breast cancer, colorectal cancer and melanoma, Pfizer. “Collectively, the data presented this year at SABCS for vepdegestrant, especially in combination with palbociclib, show the potential of this investigational innovative therapeutic option. Our ongoing collaboration with Arvinas exemplifies our shared commitment to bringing new therapies to patients with ER+/HER2- breast cancer, who may feel uncertain and vulnerable in the face of recurrent advanced disease.” Pending additional data and agreement with regulatory authorities, Arvinas and Pfizer plan to broaden development of vepdegestrant to include new combinations with cyclin-dependent kinase (CDK) inhibitors in both the first- and second-line settings. The companies plan to initiate a new second-line Phase 3 trial of vepdegestrant in combination with palbociclib and potentially other CDK4/6 inhibitors, and a new first-line Phase 3 trial of vepdegestrant plus Pfizer’s novel CDK4 inhibitor (PF-07220060). Vepdegestrant + Palbociclib Phase 1b Study In a spotlight presentation, interim data from the Phase 1b cohort of the first-in-human (FIH) ARV-471-mBC-101 study evaluating vepdegestrant in combination with palbociclib (NCT04072952) assessed the safety, tolerability and anti-tumor activity of the combination among 46 patients with heavily pre-treated locally advanced or metastatic ER+/HER2- breast cancer. At the time of data cutoff (June 6, 2023), patients had received a median of four prior therapies across all lines (median of three in the metastatic setting); 87% were previously treated with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; 80% were previously treated with fulvestrant; and 76% were previously treated with chemotherapy, including 46% in the metastatic setting. Patients were treated once daily with oral doses of vepdegestrant at 180 mg (n=2), the recommended Phase 3 dose (RP3D) of 200 mg (n=21), 400 mg (n=3) or 500 mg (n=20), plus 125 mg of palbociclib given orally once daily for 21 days, followed by seven days off treatment in 28-day cycles. Vepdegestrant in combination with palbociclib demonstrated: A clinical benefit rate (CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥ 24 weeks) of 63% (95% CI: 47.5–76.8), or 29/46 patients; at the RP3D of 200 mg (n=21), the CBR was 67% (95% CI: 43.0 – 85.4), or 14/21 patients CBR in patients with mutant ESR1: 72% (95% CI: 52.8-87.3), or 21/29 patients; at the RP3D of 200 mg (n=14), the CBR was 79% (95% CI: 49.2 – 95.3), or 11/14 patientsCBR in patients with wild-type ESR1: 53% (95% CI: 26.6-78.7), or 8/15 patients; at the RP3D of 200 mg (n=7), the CBR was 43% (95% CI: 9.9 – 81.6), or 3/7 patients An objective response rate (ORR) in evaluable patients with measurable disease at baseline (n=31) of 42% (95% CI: 24.5–60.9), or 13/31 patients; at the RP3D of 200 mg (n=15), the ORR was 53% (95% CI: 26.6 – 78.7) ORR in patients with mutant ESR1: 47% (95% CI: 23.0-72.2), or 8/17 patients ORR at the RP3D of 200 mg (n=10): 60% (95% CI: 26.2 – 87.8) ORR in patients with wild-type ESR1: 42% (95% CI: 15.2-72.3), or 5/12 patients ORR at the RP3D of 200 mg (n=5): 40% (95% CI: 26.6 – 78.7) Median progression free survival (PFS) of 11.1 months (95% CI: 8.2 – NE); 22 of 46 patients across all doses had progression events by time of data cutoff PFS in patients with mutant ESR1: 11.0 months (95% CI: 8.2-NE), 13 of 29 patients had progression events by data cutoffPFS in patients with wild-type ESR1: 11.1 months (95% CI: 2.8-NE), 8 of 15 patients had progression events by data cutoff In an assay of circulating tumor DNA (ctDNA), patients with ESR1 mutations (n=22 evaluable for ctDNA analysis after 1 cycle of treatment) demonstrated a -96.8% mean decrease (range: -75.6% to -100%) in ESR1 mutant allele fraction after 1 cycle of treatment. The safety profile of vepdegestrant plus palbociclib was manageable with palbociclib dose reductions and/or interruptions per protocol which are consistent with those described in the prescribing label. The primary toxicity associated with the vepdegestrant plus palbociclib combination was neutropenia. Grade 4 neutropenia occurred in 8 of 21 patients (38%) treated at the RP3D of vepdegestrant (200 mg) plus palbociclib 125 mg. Grade 3/4 neutropenia occurred in 89% of all patients. There was a higher occurrence of Grade 4 neutropenia, although discontinuation rates of palbociclib and rates of infection were in line with historical palbociclib data. No cases of febrile neutropenia were reported in any of the 46 patients treated with the combination. Three of 46 patients discontinued palbociclib due to neutropenia including one out of 21 treated with the RP3D of vepdegestrant (200 mg) plus palbociclib 125 mg. The majority of Grade 4 neutropenia events occurred in the first cycle of treatment and occurrences of Grade 3/4 neutropenia decreased with palbociclib dose reductions as described in the prescribing label. The safety profile was otherwise consistent with the profile of palbociclib and what has been observed in other clinical trials for vepdegestrant. An increase in palbociclib exposure (46% - 58%) was observed compared to historical pharmacokinetic (PK) data, with similar increases observed with vepdegestrant 200 mg and 500 mg QD. “While many patients I treat with ER+/HER2- breast cancer respond well to current therapies, disease progression is still an unfortunate reality and there is a significant need for additional therapies to help us treat ER+/HER2- breast cancer that has spread to other parts of the body, or metastasized,” said Erika Hamilton, M.D., director of Breast Cancer Research at Sarah Cannon Research Institute in Nashville, Tennessee, and a lead investigator in the vepdegestrant clinical program and presenting author on the data presentation at SABCS. “Vepdegestrant represents a potential new approach to degrading ER, a pathway known to drive breast cancer progression, and I am encouraged by the early data seen in the Phase 1b cohort of this study. Importantly, patients were able to utilize standard dose reductions to manage neutropenia and remain on treatment.” Additional Abstracts Presented at SABCS Together, Arvinas and Pfizer will share five additional abstracts at SABCS, including a vepdegestrant monotherapy VERITAC Phase 2 dose expansion update, a pharmacokinetic/pharmacodynamic (PK/PD) model evaluating the optimal dosing of palbociclib in combination with vepdegestrant, and three additional Trial in Progress abstracts. The VERITAC Phase 2 monotherapy dose expansion of the ARV-471-mBC-101 study analyzed the safety, efficacy, and tolerability of vepdegestrant amongst 35 heavily pre-treated patients with locally advanced or metastatic ER+/HER2- breast cancer. This update includes 12 months of additional follow-up data, and the tolerability and efficacy profile remained largely consistent with previous data disclosures. In the PK/PD model simulation, a 100 mg dose of palbociclib in combination with vepdegestrant produced similar incidence of Grade 4 neutropenia and comparable average palbociclib exposure compared to historical reference. Titles for the five additional abstracts are listed here. Investor Call & Webcast Details A conference call and webcast will be held with executives from Arvinas and Pfizer to discuss the data presented at SABCS. Details for this call will be provided in a separate press release shared on www.arvinas.com. Participants are invited to listen by going to the Events and Presentation section under the Investors page on the Arvinas website at www.arvinas.com. A replay of the webcast will be archived on the Arvinas website following the presentation. About vepdegestrant (ARV-471)Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits. Ongoing and planned clinical trials will continue to monitor and evaluate the safety and anti-tumor activity of vepdegestrant. About ArvinasArvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC targeted protein degraders, that are designed to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. In addition to its robust preclinical pipeline of PROTAC protein degraders against validated and “undruggable” targets, the company has three investigational clinical-stage programs: ARV-766 and bavdegalutamide for the treatment of men with metastatic castration-resistant prostate cancer; and vepdegestrant (ARV-471) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer. Arvinas, as part of its overall business strategy, selectively assesses opportunities for potential collaboration, license, marketing and royalty arrangements, and similar transactions, to advance and accelerate the development and enhance the commercial potential of its product candidates. For more information, visit www.arvinas.com. Arvinas Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential advantages and therapeutic benefits of vepdegestrant (ARV-471), as well as other statements with respect to vepdegestrant, including the presentation and/or publication of data from vepdegestrant trials. All statements, other than statements of historical facts, contained in this press release are forward-looking statements. The words “believe,” “expect,” “may,” “plan,” “potential,” “will,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make as a result of various risks and uncertainties, including but not limited to: our and Pfizer, Inc.’s (“Pfizer”) performance of our respective obligations with respect to our collaboration with Pfizer; whether we and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant and obtain marketing approval for and commercialize vepdegestrant on our current timelines or at all; whether our cash and cash equivalent resources will be sufficient to fund our foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other important factors discussed in the “Risk Factors” section of our Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent other reports on file with the Securities and Exchange Commission. The forward-looking statements contained in this press release reflect our current views with respect to future events, and we assume no obligation to update any forward-looking statements except as required by applicable law. These forward-looking statements should not be relied upon as representing our views as of any date after the date of this release. About IBRANCE® (palbociclib) 125 mg tablets and capsulesIBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression.2,3 In the U.S., IBRANCE is a prescription medicine indicated for the treatment of adults with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as the first hormonal based therapy; or with fulvestrant in people with disease progression following hormonal therapy. The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here. IMPORTANT IBRANCE®(palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever. Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with CDK4/6 inhibitors, including IBRANCE when taken in combination with endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2, PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported. Additional cases of ILD/pneumonitis have been observed in the post-marketing setting, with fatalities reported. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who have new or worsening respiratory symptoms and are suspected to have developed pneumonitis, interrupt IBRANCE immediately and evaluate the patient. Permanently discontinue IBRANCE in patients with severe ILD or pneumonitis. Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients to consider sperm preservation before taking IBRANCE. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants. The most common adverse reactions(≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%). The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%). Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%). The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%). The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%). Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%). Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure. For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis. About Pfizer OncologyAt Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood and lung cancers, as well as melanoma. About Pfizer: Breakthroughs That Change Patients’ LivesAt Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Pfizer Disclosure Notice:The information contained in this release is as of December 5, 2023. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about vepdegestrant (ARV-471), IBRANCE® (palbociclib) and a global collaboration between Pfizer and Arvinas to develop and commercialize vepdegestrant, including their potential benefits and plans for clinical trials, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from the clinical studies; whether and when any applications may be filed for vepdegestrant, IBRANCE or any potential combinations for any potential indications in any jurisdictions; whether and when regulatory authorities may approve any potential applications that may be filed for vepdegestrant, IBRANCE or any potential combinations in any jurisdictions, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether vepdegestrant, IBRANCE or any potential combinations will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of vepdegestrant, IBRANCE or any potential combinations; whether the collaboration between Pfizer and Arvinas will be successful; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. Arvinas Contacts Investor Contact:Jeff Boyle, Arvinas Investor Relations347-247-5089Jeff.Boyle@arvinas.com Media Contact:Kirsten Owens, Arvinas Communications203-584-0307Kirsten.Owens@arvinas.com Pfizer Contacts Investor Contact:+1 (212) 733-4848IR@pfizer.com Media Contact:+1 (212) 733-1226PfizerMediaRelations@pfizer.com 1 IBRANCE® (palbociclib) Prescribing Information. New York. NY: Pfizer Inc: 2022.2 Weinberg, RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science; 2014:275-329.3 Sotillo E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22.

Novartis has joined Cancer Research UK as the second major pharmaceutical company to partner in the charity’s determining extended therapeutic indications for existing drugs in rare molecularly-defined indications using a national evaluation (DETERMINE) trial. The trial was launched in November this year and enrolled paediatric and adult patients diagnosed with any rare cancer type with its focus on evaluating the multi-drug, precision medicine for rare cancers. The study was launched by Cancer Research UK’s Centre for Drug Development, the University of Manchester and Roche. With Novartis on board, Roche will continue providing access to cancer treatments via the study, supported by sponsorship and management from the Centre for Drug Development and trial leadership from the University of Manchester. The DETERMINE trial is focused on discovering whether existing drugs – including those which are licensed for more common types of cancer – could also benefit patients diagnosed with rare cancer types that the drug is not currently licensed for. Eligible patients will have taken part in genetic screening and will have had one of the particular genetic mutations detected in their cancer that can be targeted by a drug on the trial. Cancer Research UK has encouraged other pharmaceutical or biotechnology companies with targeted oncology agents which have been licensed or are close to being licensed, with the trial offering a chance to assess their agent in rare indications not included in their licence. With more companies involved, further access will be opened up to even more patients with rare cancers, offering them a chance of finding a potentially beneficial treatment. Any treatment that appears to be benefitting patients on the trial will be submitted for review by the Cancer Drugs Fund (CDF). It is then down to a decision made by the CDF, working in tandem with NHS England Clinical Policy team, as to whether a period of data collection in the CDF is appropriate in order to assess if the drug could be used as a routine treatment option on the NHS for patients with this cancer type. The Christie NHS Foundation Trust has been the first site to host the trial, with other sites soon to follow. This includes the Royal Marsden NHS Foundation Trust, the University of Glasgow and the University of Birmingham, as well as facilities across the entire adult and paediatric Experimental Cancer Medicine Centres network. Dr Gerrit Zijlstra, chief medical officer, Novartis UK, said: “At Novartis we are committed to reimagining medicine, and we are delighted to partner with Cancer Research UK and the University of Manchester to explore further potential of our innovative treatments in changing outcomes for adults, teenagers and children with rare cancers.”

Patients treated in dose-escalation portion of Phase 1/2 study evaluating seclidemstat in combination with azacitidine 50% overall response rate among eight myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients who relapsed or progressed after hypomethylating agent therapy HOUSTON, Dec. 13, 2022 (GLOBE NEWSWIRE) -- Salarius Pharmaceuticals Inc. (NASDAQ: SLRX), a clinical-stage biopharmaceutical company using protein inhibition and protein degradation to develop cancer therapies for patients in need of new treatment options, today announced that investigators in the Department of Leukemia at the University of Texas MD Anderson Cancer Center presented clinical data on seclidemstat in patients with MDS and CMML at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition underway in New Orleans and virtually. Seclidemstat is a novel oral, reversible, targeted LSD1 inhibitor. The poster was presented by Guillermo Montalban-Bravo, M.D. of the Department of Leukemia and is available in the Investors Events and Presentations section of Salarius’ website here. The objective of this investigator-initiated Phase 1/2 dose-escalation study is to evaluate the safety, tolerability, maximum tolerated dose and overall response of seclidemstat in combination with azacitidine in adult patients with higher-risk MDS or CMML who previously failed or relapsed after hypomethylating agent therapy. As of October 2022, nine patients were enrolled with a median follow-up time of 3.9 months. Typically, overall survival is four to six months for patients after failing therapy with hypomethylating agents. As presented at ASH, no serious adverse events were reported and all adverse events observed in the study were manageable. Of the eight evaluable patients, four (50%) had an objective response including one complete response patient who is planned to receive potentially curative allogeneic stem cell transplantation, two marrow complete responses plus hematological improvement and one marrow complete response. The Phase 1 dose-escalation portion of this study will evaluate up to six dose levels of seclidemstat. The maximum tolerated dose, which will inform the Phase 2 portion of the study, was not yet reached. “We are encouraged that this investigator-initiated trial, which is separate from Salarius’ sponsored sarcoma trial, shows promising results at this early stage of the study when seclidemstat is combined with azacitidine,” said David Arthur, president and chief executive officer of Salarius Pharmaceuticals. “Patients who have failed prior treatments including hypomethylating agents typically have an overall survival of four to six months and are in desperate need of new treatment options. With a 50% overall response rate, including a complete remission planned for potential curative allogeneic stem cell transplantation, we are hopeful that seclidemstat will play a role in their treatment paradigm.” Mr. Arthur added, “In mid-October enrollment in this investigator-initiated trial was voluntarily paused in response to a suspected unexpected serious adverse reaction, or SUSAR, in Salarius’ FET-rearranged portion of our Phase 1/2 sarcoma study. We are working with the FDA to further analyze the available data with the goal of understanding how best to proceed and restart enrollment across both seclidemstat clinical trials.” About Salarius Pharmaceuticals Salarius Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing therapies for patients with cancer in need of new treatment options. Salarius’ product portfolio includes seclidemstat, the company’s lead candidate, which is being studied as a potential treatment for pediatric cancers, sarcomas and other cancers with limited treatment options, and SP-3164, an oral small molecule protein degrader. Seclidemstat is currently in a Phase 1/2 clinical trial for relapsed/refractory Ewing sarcoma and certain additional sarcomas that share a similar biology. This trial is currently on a partial clinical hold and is not enrolling new patients. Seclidemstat has received fast track, orphan drug and rare pediatric disease designations for Ewing sarcoma from the U.S. Food and Drug Administration. Salarius is also exploring seclidemstat’s potential in several cancers with high unmet medical need, with an investigator-initiated Phase 1/2 clinical study in hematologic cancers at MD Anderson Cancer Center. This trial is currently on a voluntary pause and is not enrolling new patients. Salarius has received financial support from the National Pediatric Cancer Foundation to advance the Ewing program and was a recipient of a Product Development Award from the Cancer Prevention and Research Institute of Texas (CPRIT). SP-3164 is currently in IND-enabling studies and anticipated to enter the clinic in 2023. For more information, please visit salariuspharma.com or follow Salarius on Twitter and LinkedIn. Forward-Looking Statements This announcement and the referenced presentation contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation are forward-looking statements. These forward-looking statements may be identified by terms such as “will,” “future,” “believe,” “developing,” “expect,” “may,” “progress,” “potential,” “could,” “look forward,” “encouraged,” “hopeful,” “promising,” “anticipate,” “might,” “should,” and similar terms or expressions or the negative thereof. Examples of such statements include, but are not limited to, statements relating to the following: the advantages of seclidemstat (SP-2577) as a treatment for Ewing sarcoma, Ewing-related sarcomas, and other cancers and its ability to improve the life of patients; expected cohort readouts from the company’s clinical trials and expected therapeutic options for SP-2577 and related effects and projected efficacy, including SP-2577’s ability to inhibit LSD1; the future of the company’s Phase 1/2 trial of seclidemstat as a treatment for Ewing sarcoma and FET-rearranged sarcomas following the recently announced suspected unexpected severe adverse reaction (SUSAR) event and resulting partial clinical hold by the U.S. Food and Drug Administration (FDA); the advantages of protein degraders including the value of SP-3164 as a cancer treatment; the timing of clinical trials for SP-3164 and expected therapeutic options for SP-3164 and related effects and projected efficacy; the impact that the addition of new clinical sites will have on the development of our product candidates; the timing of our IND submissions to the FDA and subsequent timing for initiating clinical trials; interim data related to our clinical trials, including the timing of when such data is available and made public; our growth strategy; whether the company will develop additional undisclosed cancer-fighting assets in the targeted protein degradation space; expanding the scope of our research and focus to high unmet need patient populations; and the commercial or market opportunity and expansion for each therapeutic option, including the availability and value of a pediatric priority review voucher for in-clinic treatments and potential for accelerated approval. We may not actually achieve the plans, carry out the intentions or meet the expectations or objectives disclosed in the forward-looking statements. You should not place undue reliance on these forward-looking statements. These statements are subject to risks and uncertainties which could cause actual results and performance to differ materially from those discussed in the forward-looking statements. These risks and uncertainties include, but are not limited to, the following: Seclidemstat’s impact in Ewing sarcoma and as a potential new and less-toxic treatment; expected dose escalation and dose expansion; resolution of the FDA’s partial clinical hold on the company’s Phase 1/2 trial of seclidemstat as a treatment for Ewing sarcoma and FET-rearranged sarcomas following the SUSAR; our ability to resume enrollment in the clinical trial following its review of the available data surrounding the SUSAR; the adequacy of our capital to support our future operations and our ability to successfully initiate and complete clinical trials and regulatory submissions; the ability of, and need for, us to raise additional capital to meet our business operational needs and to achieve its business objectives and strategy; future clinical trial results and the impact of such results on us; that the results of studies and clinical trials may not be predictive of future clinical trial results; risks related to the drug development and the regulatory approval process; the competitive landscape and other industry-related risks; and other risks described in our filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2021, as revised or supplemented by its Quarterly Reports on Form 10-Q and other documents filed with the SEC. The forward-looking statements contained in this announcement and the referenced presentation speak only as of the date of this announcement and the referenced presentation and are based on management’s assumptions and estimates as of such date. We disclaim any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. CONTACT: LHA Investor Relations Kim Sutton Golodetz kgolodetz@lhai.com 212-838-3777