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BARCELONA — One of this weekend’s sleeper data presentations at Europe’s biggest oncology conference puts Pfizer in a leading position in a common cancer condition with no approved treatments in the US or Europe. The New York-based pharma giant’s GDF-15-directed monoclonal antibody helped cancer patients gain weight and, at the highest dose, experience improvements in appetite, physical activity and muscle mass in a Phase 2 trial, according to data presented at the European Society for Medical Oncology confab on Saturday. Analysts at Leerink Partners think the experimental medicine, code-named ponsegromab, has blockbuster potential. But the large pharma has many questions to work through before it can mount a registrational study next year for ponsegromab in cancer cachexia, a muscle-wasting condition that leads to severe weight loss and impacts a patient’s ability to tolerate cancer medications. Patients with cachexia also require more healthcare resources, leading to a “high clinical and economic burden,” according to another Pfizer-funded study presented at ESMO. Doctors have long sought a treatment for the metabolic condition, which some research suggests may be linked to up to 30% of cancer deaths. It’s also a strain on patients with chronic conditions like heart failure and chronic obstructive pulmonary disease, among others. The broad potential gives ponsegromab a shot at achieving sales of $1 billion or more, Leerink Partners analyst David Risinger wrote in a Sunday evening note. Despite its prevalence, though, the condition has not received “the attention it deserves,” Min Li, a professor and co-leader of the cancer biology program at the Stephenson Cancer Center in Oklahoma, said in an email. “We are now more confident in saying that we can see the light at the end of the tunnel,” Li said in the days after the ESMO presentation and simultaneous publication of the Phase 2 data in the New England Journal of Medicine . Having one of the world’s biggest pharma companies with ample R&D resources to approach late-stage testing could be a boon for the field. “Incredible progress is finally being made in this space, and we very much hope that Pfizer’s findings continue to be positive and pave the way for more successful trials to follow,” Andy Judge, a University of Florida professor and president of the Cancer Cachexia Society, told Endpoints in an email. Cachexia comes with a lot of complexities, likely leading to a challenging Phase 3 showdown for Pfizer. The company anticipates launching the trial next year and it still needs to hash out plans with regulators, according to a spokesperson, who said Pfizer will share more Phase 3 details at a later date. The condition is quite heterogeneous and impacts different cancers at varying rates, which could make it difficult to prove a treatment works in late-stage trials. Li noted that “there is no consensus on the optimal endpoint to evaluate cancer cachexia.” Another biotech, NGM Bio, warned in recent years of the lack of a clear regulatory path for cachexia. Another company received approval in Japan in 2020 for the medicine anamorelin, but the ghrelin receptor agonist was rejected in Europe a few years before. Also standing in the way is the number of organs and tissues involved in the systemic dysfunction. Going after a single pathway “has yielded limited efficacy,” Li said. Pfizer’s ponsegromab goes after growth differentiation factor 15, or GDF-15. The company’s researchers have said neutralizing GDF-15 could lead to improvements in caloric intake and boost physical activity. The candidate was discovered in-house and first entered the clinic in a 2018 healthy volunteer trial. Ponsegromab is also being tested in patients with heart failure . That study is enrolling patients with cardiac cachexia or fatigue in its main cohort and is expected to be completed next March, according to the federal trials database. Li noted other potential pathways in cancer cachexia could be targeted, such as “myostatin/activin signaling, IL-6, ghrelin, circular RNAs, metabolic enzymes, TNF and TGF.” Meanwhile, more studies are needed to “directly prove” that stabilizing muscle and fat reserves, “or even revers[ing] those losses,” has a direct impact on patient outcomes, Michael Rosenthal, assistant director of radiology at Dana-Farber/Brigham and Women’s Hospital, said in an email. Aside from the effects on weight, doctors will look for impacts on daily activities. “It would be impressive to see improvement in ECOG performance status and overall survival in a randomized trial of chemotherapy with or without ponsegromab,” Vincent Chung, a medical oncologist at City of Hope, said in an email. ECOG is a scale that assesses a patient’s ability to function, including walking and self-care activities. Pfizer is in the lead in cachexia drug development, and it’s no stranger to breaking open fields, having done so in areas like ATTR-CM, where it could soon face competition. Other drugmakers looking at cachexia include UK-based Actimed Therapeutics, Tokyo-based TMS and Vistagen, which says on its website that it is “evaluating the path forward” for its candidate for more Phase 2 development. Even if those medicines make it to market, it’s still important to think about treating cachexia in a “multi-dimensional way, rather than a single drug,” David Hui, director of supportive and palliative care research at the University of Texas MD Anderson Cancer Center, said in an interview on the sidelines of ESMO. Doctors currently work with a team of healthcare professionals to address cachexia with diet and exercise and medications to treat symptoms of pain, difficulty swallowing and other complications, he said. “Having the dietitian, physical therapy and supportive palliative care team working side by side together with the patient and family can, hopefully, lead to improved outcomes because everyone may have different concerns related to cachexia,” Hui said.

BARCELONA — At a major cancer conference, Pfizer made an unexpected announcement : It has late-stage plans in weight management. But it’s not targeting weight loss like one would first think amid the drug industry’s current fixation on obesity. While industry insiders and investors have eagerly awaited updates on Pfizer’s obesity programs, the New York pharma giant is now advancing a drug on the other end of the weight management spectrum. The drugmaker said Saturday it plans to take a GDF15-directed monoclonal antibody, named ponsegromab, into registration-enabling testing next year for cancer patients with cachexia, a condition that can lead to muscle wasting and life-threatening weight loss in patients with cancer. The decision to move into a registration-enabling study — plans of which are still pending discussions with regulators, according to a Pfizer spokesperson — is based on Phase 2 data presented in a late-breaking paper this weekend at the annual European Society for Medical Oncology confab in Barcelona. Ponsegromab was tested in a Phase 2 of 187 patients with non-small cell lung cancer, pancreatic cancer and colorectal cancer, and trial investigators looked at change from baseline in body weight as the primary endpoint. After 12 weeks, Pfizer said the experimental drug met the primary endpoint as there were “significant and robust increases” in patients’ body weight across all doses (100 mg, 200 mg and 400 mg) compared to placebo. At the highest dose, patients reached a 5.6% mean increase in body weight, according to Pfizer. The company said there were “no clinically significant adverse trends noted with ponsegromab administration.” Treatment-related adverse events happened in 8.9% of patients on placebo and 7.7% of patients on Pfizer’s drug. The highest dose also showed improvements on measures of appetite, physical activity and muscle mass, Pfizer said. “These results provide strong evidence that we have unlocked a mechanism to interrupt a critical driver of cachexia, GDF-15, which has the potential to impact patients with cancer cachexia and other life-threatening conditions,” Charlotte Allerton, head of discovery and early development at Pfizer, said in a statement. She highlighted that ponsegromab was discovered internally. “We look forward to advancing this program as part of our broader cardiometabolic portfolio to address weight management across the spectrum of patient needs.” There’s no FDA-approved treatment for cancer cachexia. In Japan, ONO Pharmaceutical markets Adlumiz. Also known as anamorelin, the tablet received a 2020 greenlight in that country after being rejected in Europe three years prior. It’s a ghrelin receptor agonist, which works by drumming up pathways involved in appetite and metabolism. The Cleveland Clinic estimates about 9 million people worldwide are affected by the condition. In addition to cancer, cachexia can also be a complication of Alzheimer’s, dementia, obstructive pulmonary disease and heart failure. Pfizer is also testing ponsegromab in a separate Phase 2 in patients with heart failure who have elevated serum concentrations of GDF-15. Other biotechs are also looking at GDF-15. German startup CatalYm raised $150 million this summer to test its GDF15-neutralizing antibody for solid tumors, and formerly public NGM Bio raised $122 million in July to test a GDF15/GFRAL antagonist for a rare condition known as hyperemesis gravidarum. Novartis shelved its GDF-15 agonist last year.

- Top-line data with unexpected results requiring further clarification, did not meet primary endpoint as per protocol - Potent growth hormone release following macimorelin stimulation - Safety of macimorelin confirmed in the pediatric population TORONTO, ONTARIO, Aug. 27, 2024 (GLOBE NEWSWIRE) -- COSCIENS Biopharma Inc. (NASDAQ: CSCI) (TSX: CSCI) (“COSCIENS” or the “Company”), a specialty biopharmaceutical company developing and commercializing a diversified portfolio of pharmaceutical and diagnostic products and active ingredients for healthcare and cosmetics industries, today announced the top-line results of its Phase 3 safety and efficacy study AEZS-130-P02 (the "DETECT-trial") evaluating macimorelin for the diagnosis of Childhood Onset Growth Hormone Deficiency ("CGHD"). While top-line data show that macimorelin repeatedly demonstrated its capacity to stimulate growth hormone release as required to perform a growth hormone stimulation test, the primary efficacy endpoint for the DETECT-trial has not been met according to the definitions in the study protocol. In the study, the macimorelin test was compared to current standard growth hormone stimulation tests (arginine and clonidine). Although further analysis of the study results is required, initial review of the results indicates that the comparator tests may have led to a high false positive rate which impacted macimorelin’s ability to reach the primary efficacy endpoint. These unexpected results require further clarification and some re-analyses with the aim to consider the trial outcome and the strategy moving forward. The DETECT-trial was an international, multicenter safety and efficacy trial on macimorelin in a dose of 1.0 mg/kg body weight. The trial was conducted at clinical sites across the USA, Armenia, Georgia, Germany, Italy, Serbia, Slovakia, Poland, Romania, and Turkey. Following the screening period of Visit 1, the macimorelin test was conducted at Visit 2 and repeated at Visit 5, with blood samples being taken for Pharmacokinetic (PK) and Pharmacodynamic (PD) data at predefined times. At Visit 3 and Visit 4, an arginine test and a clonidine test were performed in a randomized order as standard growth hormone stimulation tests (GHSTs) to be compared with macimorelin. Visit 6 was a safety follow-up at study end. An independent external expert panel had been established to adjudicate the final growth hormone deficiency status of a child (i.e., child ill or child healthy) based on all medical data collected as well as the outcome of the two standard GHSTs. “The top-line results confirm the excellent safety of macimorelin, similar to what was demonstrated in our clinical and commercial experience with the use of macimorelin to diagnose adult growth hormone deficiency (AGHD). However, it was surprising to see that many subjects, who had been adjudicated as ill (growth hormone deficient) according to the comparator tests arginine and clonidine, showed high growth hormone stimulation following macimorelin. Our team will be further analyzing the detailed data from the DETECT-trial to gain insights into the reasons behind these unexpected results” commented Nicola Ammer, Chief Medical Officer of the Company. The completed study enrolled 102 subjects aged 3 to 17 years. The outcome of an independent adjudication of each subject was used to define the “true” GHD status (i.e., child ill or child healthy) at the end of the trial. Based on this, top-line data present an ‘optimal’ growth hormone (GH) cut-off point of 25.59 ng/mL, which is substantially higher than the standard cut-off points of 7-10 ng/mL as defined in current guidelines with existing tests. This surprisingly high cut-off point leads to a failure in the sensitivity and specificity assessments. Sensitivity as well as specificity are important parameters characterizing the performance of a diagnostic test, as they show a test’s capabilities to identify ill subjects as being ill (sensitivity) and to identify healthy subjects as being healthy (specificity), respectively. “While we expect the top-line data of our DETECT-trial to be further analyzed and discussed with health authorities, macimorelin is approved in the USA and continues to be marketed in Europe for AGHD. As we get the results of further analysis of the DETECT-trial we will be considering our action plan for macimorelin. In addition, we will continue our ongoing review and prioritization process for COSCIENS’ pipeline. Our goal remains to focus our resources and cash on those programs and products that we believe will propel the Company to its next phase of growth as a diversified biopharmaceutical company,” added Gilles Gagnon, Chief Executive Officer of the Company. “We would like to thank everyone involved in the DETECT-trial and especially the extraordinary engagement of the children enrolled in the study and their parents, as well as the excellent efforts of the clinical sites and our team members involved.” The DETECT-trial was the second study needed to evaluate the potential use of macimorelin as diagnostic test in children as agreed upon with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the Company's Pediatric Investigation Plan. Full trial result reporting is expected to occur later this year. For more information about the DETECT-trial, please visit EU Clinical Trials Register and reference EudraCT #2018-001988-23 and clinicaltrials.gov identifier NCT04786873. About Macimorelin (Macrilen®; GHRYVELIN®) Macimorelin, an oral drug used for the diagnosis of adult growth hormone deficiency (AGHD) is approved for marketing under the brand name GHRYVELIN® in the European Economic Area and Macrilen® in the United States, South Korea and Israel. Macimorelin (Macrilen®; GHRYVELIN®), a ghrelin receptor agonist, is an orally administered peptidomimetic molecule that stimulates the secretion of growth hormone from the pituitary gland. Stimulated growth hormone levels are measured in blood samples taken after oral administration of macimorelin for the assessment of AGHD. Approval of macimorelin for use in adult was granted by the FDA in 2017 and by the EMEA in 2019, based on Phase III data showing that oral macimorelin provides accuracy comparable to that of standard insulin tolerance testing (ITT), but has a more favorable safety profile compared to ITT. Oral macimorelin also reduces false positive test results, helping to avoid unnecessary treatment of patients. About COSCIENS Biopharma Inc. COSCIENS is a specialty biopharmaceutical company engaged in the development and commercialization of a diverse portfolio of pharmaceutical and diagnostic products, including those focused on areas of significant unmet medical need. One of CONSCIENS’ lead products is macimorelin (Macrilen®; Ghryvelin®), the first and only U.S. FDA and European Medicines Agency approved oral test indicated for the diagnosis of adult growth hormone deficiency (AGHD). COSCIENS is also engaged in the development of therapeutic assets and proprietary extraction technology, which is applied to the production of active ingredients from renewable plant resources currently used in cosmeceutical products (i.e., oat beta glucan and avenanthramides which are found in leading skincare product brands like Aveeno and Burt’s Bees formulations) and being developed as potential nutraceuticals and/or pharmaceuticals. The company is listed on the NASDAQ Capital Market and the Toronto Stock Exchange, and trades on both exchanges under the ticker symbol “CSCI”. For more information, please visit COSCIENS’ website at www.cosciensbio.com. Forward-Looking Statements The information in this news release has been prepared as of August 27, 2024. Certain statements in this news release, referred to herein as "forward-looking statements", constitute "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995, as amended, and "forward-looking information" under the provisions of Canadian securities laws. All statements, other than statements of historical fact, that address circumstances, events, activities, or developments that could or may or will occur are forward-looking statements. When used in this news release, words such as "anticipate", "assume", "believe", "could", "expect", "forecast", "future", "goal", "guidance", "intend", "likely", "may", "would" or the negative or comparable terminology as well as terms usually used in the future and the conditional are generally intended to identify forward-looking statements, although not all forward-looking statements include such words. Forward-looking statements in this news release include, but are not limited to, statements relating to: the timing for the release of the full results from the DETECT-trial; our consideration of our action plan for macimorelin; and our ongoing review and prioritization process for COSCIENS’ pipeline. Forward-looking statements are necessarily based upon a number of factors and assumptions that, while considered reasonable by the Company as of the date of such statements, are inherently subject to significant business, economic, operational and other risks, uncertainties, contingencies and other factors, including those described below, which could cause actual results, performance or achievements of the combined Company to be materially different from results, performance or achievements expressed or implied by such forward-looking statements and, as such, undue reliance must not be placed on them. Forward-looking statements involve known and unknown risks and uncertainties which include, among others: the combined Company’s present and future business strategies; operations and performance within expected ranges; anticipated future cash flows; local and global economic conditions and the environment in which the combined Company operates; anticipated capital and operating costs; uncertainty in our revenue generation from our marketed products, product development and related clinical trials and validation studies, including as a result of the DETECT-trial for Macrilen™ (macimorelin) not meeting its primary endpoint; results from our other products under development may not be successful or may not support advancing the product; our ability to raise capital and obtain financing to continue our currently planned operations; our now heavy dependence on sales by and revenue from our main distributor of our legacy Ceapro products (including AVA and OBG) and its customers; the continued availability of funds and resources to successfully commercialize products; the ability to secure strategic partners for late stage development, marketing, and distribution of our products, including our ability to enter into a new license agreement or similar arrangement following the termination of the license agreement with Novo Nordisk AG for rights to Macrilen™ in North America; our ability to enter into out-licensing, development, manufacturing, marketing and distribution agreements with other pharmaceutical companies and keep such agreements in effect; our ability to protect and enforce our patent portfolio and intellectual property; and our ability to continue to list our common shares on the NASDAQ Capital Market. Investors should consult our quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties, including those discussed in our Annual Report on Form 20-F and MD&A filed under the Company’s profile on SEDAR+ at www.sedarplus.ca and on EDGAR at www.sec.gov. We disclaim any obligation to update any such risks or uncertainties or to publicly announce any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments, unless required to do so by a governmental authority or applicable law. No securities regulatory authority has either approved or disapproved of the contents of this news release. The Toronto Stock Exchange accepts no responsibility for the adequacy or accuracy of this news release. Issuer: Gilles R. GagnonPresident & CEOggagnon@ceapro.com+1 (780) 421-4555 Investor Contact: Jenene ThomasJTC TeamT (US): +1 (833) 475-8247E: csci@jtcir.com