Ipsen Biopharmaceuticals, Inc.

Using Marengo’s TriSTAR platform, Ipsen and Marengo teams expand their ongoing oncology research to include up to two additional assets in new early development collaborationResearch will focus on using Marengo’s TriSTAR platform to reinvigorate and mobilize selective Vβ T cells to boost anti-tumor activity in patients with traditionally difficult-to-treat ‘cold’ tumors PARIS, FRANCE, and CAMBRIDGE, MA, U.S., 07 June 2024 - Ipsen (Euronext: IPN; ADR: IPSEY) and Marengo Therapeutics Inc, a clinical-stage biotech company, announced today the expansion of their ongoing oncology research partnership, to include TriSTAR, Marengo’s next-generation, precision T cell engager (TCE) technology. Traditional TCEs targeting ‘cold’ tumors have limited efficacy due to poor T cell quality and exhaustion. Marengo’s proprietary first-in-class TriSTAR TCEs have the potential to overcome these limitations, redirecting a new and expanded pool of highly activated memory Vβ T cells to the tumor. The teams will focus on exploring potential in ‘cold’ tumors which typically fail to trigger a strong immune response when treated with TCEs. “We take a science-first approach to expanding our pipeline and are delighted to continue our strong work with the teams at Marengo, who share our passion and drive to accelerate cancer innovations,” said David Jenkins, SVP, Research and External Innovation at Ipsen. “Through Marengo’s next-generation TriSTAR platform we have the potential to unlock the power of the immune system, activating a wider pool of T cells to eradicate tumors that traditionally have a weak response to T-cell immunotherapies.” “We are excited to build on our existing research collaboration with Ipsen, which has already successfully delivered the first development candidate earlier this year,” said Zhen Su, CEO of Marengo Therapeutics. “This new collaboration with Ipsen builds on our clinically validated TCR Vβ platform and our internal work with new TriSTAR T cell engagers that suggest best-in-class potential and the ultimate precision IO goal of delivering the right T cells to the right tumor. The TriSTAR platform significantly expands our portfolio to target difficult-to-treat ‘cold’ tumors, and we are thrilled to partner with the Ipsen oncology team to realize this ambition together.” Under the terms of the agreement, Ipsen will assume responsibility for all activities following development candidate nomination. Marengo will receive an upfront payment and potential payments up to a total of $1.2 billion if all milestones are met in addition to tiered sales royalty payments. ENDS About Ipsen We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience. Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries. Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com. About Marengo Marengo Therapeutics, Inc, a clinical-stage biotech company, develops novel TCR-targeting antibodies that selectively modulate common and disease-specific T cell subsets of the germline TCR repertoire to provide lifelong protection against cancer and other diseases. With a passionate team of dedicated scientists experienced in immunology and oncology, Marengo’s proprietary Selective T Cell Activation Repertoire (STAR) platform leverages an extensive biological understanding of T cell function and receptor signaling to create a world in which everyone’s immune system can defeat cancer. To learn more, visit marengotx.com. About TriSTAR Platform Marengo’s TriSTAR platform is a multi-specific antibody-fusion platform derived from Marengo’s proprietary library of antibodies targeting germline-encoded variable Vβ regions of the TCR, fused to a T cell co-stimulatory moiety and a tumor-associated antigen binder. By expanding and redirecting a new pool of highly activated memory Vβ T cells, TriSTAR TCEs have the potential to overcome the effects of poor T cell quality and T cell exhaustion that may limit the activity of traditional TCEs. Email: corporate.communications@ipsen.com Ipsen contacts Investors Craig Marks | + 44 7584 349 193 Nicolas Bogler | +33 (0) 6 52 19 98 92 Media Amy Wolf | +41 7 95 76 07 23 Jess Smith | + 44 7557 267 634 Marengo contacts Investors Svetlana Makhni | smakhni@marengotx.com Media Peg Rusconi | peg.rusconi@vergescientific.com Disclaimers and/or Forward-Looking StatementsThe forward-looking statements, objectives and targets contained herein are based on Ipsen’s management strategy, current views and assumptions. Such statements involve known and unknown risks and uncertainties that may cause actual results, performance or events to differ materially from those anticipated herein. All of the above risks could affect Ipsen’s future ability to achieve its financial targets, which were set assuming reasonable macroeconomic conditions based on the information available today. Use of the words ‘believes’, ‘anticipates’ and ‘expects’ and similar expressions are intended to identify forward-looking statements, including Ipsen’s expectations regarding future events, including regulatory filings and determinations. Moreover, the targets described in this document were prepared without taking into account external-growth assumptions and potential future acquisitions, which may alter these parameters. These objectives are based on data and assumptions regarded as reasonable by Ipsen. These targets depend on conditions or facts likely to happen in the future, and not exclusively on historical data. Actual results may depart significantly from these targets given the occurrence of certain risks and uncertainties, notably the fact that a promising medicine in early development phase or clinical trial may end up never being launched on the market or reaching its commercial targets, notably for regulatory or competition reasons. Ipsen must face or might face competition from generic medicine that might translate into a loss of market share. Furthermore, the research and development process involves several stages each of which involves the substantial risk that Ipsen may fail to achieve its objectives and be forced to abandon its efforts with regards to a medicine in which it has invested significant sums. Therefore, Ipsen cannot be certain that favorable results obtained during preclinical trials will be confirmed subsequently during clinical trials, or that the results of clinical trials will be sufficient to demonstrate the safe and effective nature of the medicine concerned. There can be no guarantees a medicine will receive the necessary regulatory approvals or that the medicine will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Other risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation; global trends toward healthcare cost containment; technological advances, new medicine and patents attained by competitors; challenges inherent in new-medicine development, including obtaining regulatory approval; Ipsen’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Ipsen’s patents and other protections for innovative medicines; and the exposure to litigation, including patent litigation, and/or regulatory actions. Ipsen also depends on third parties to develop and market some of its medicines which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to Ipsen’s activities and financial results. Ipsen cannot be certain that its partners will fulfil their obligations. It might be unable to obtain any benefit from those agreements. A default by any of Ipsen’s partners could generate lower revenues than expected. Such situations could have a negative impact on Ipsen’s business, financial position or performance. Ipsen expressly disclaims any obligation or undertaking to update or revise any forward-looking statements, targets or estimates contained in this press release to reflect any change in events, conditions, assumptions or circumstances on which any such statements are based, unless so required by applicable law. Ipsen’s business is subject to the risk factors outlined in its registration documents filed with the French Autorité des Marchés Financiers. The risks and uncertainties set out are not exhaustive and the reader is advised to refer to Ipsen’s latest Universal Registration Document, available on ipsen.com. Attachment Ipsen PR_Marengo_07062024

Pictured: 3D image of liver damage/iStock, Mohammed Haneefa Nizamudeen Gilead Sciences announced Wednesday that its drug candidate seladelpar has shown improvement in a late-stage trial of patients with the rare liver disease primary biliary cholangitis. However, rival Ipsen Biopharmaceuticals could beat Gilead to the U.S. market. Data from the Phase III ASSURE trial in primary biliary cholangitis (PBC), showed “rapid and sustained” improvement in patients treated with Gilead’s seladelpar, a peroxisome proliferator-activated receptor delta (PPAR) agonist. This included high rates of normalization of liver biomarkers and a clinically meaningful reduction in pruritus, or itch. According to Gilead, 70% of patients met the composite response endpoint, which includes having alkaline phosphatase (ALP) levels below 1.67x the upper limit of normal (ULN), as well as a decrease in ALP levels of at least 15% and total bilirubin levels at or below the ULN. In addition, 42% of patients reached ALP normalization at 24 months, a marker of liver disease progression. Patients had also reached “sustained improvement” in pruritus, with a mean reduction of 3.8 and 3.1 points on the numerical rating scale at 12 months and 24 months, respectively. “The long-term efficacy and safety interim results from ASSURE demonstrate that seladelpar may meaningfully raise the bar in PBC. Seladelpar can help people achieve significant reduction, and in some cases, normalization of liver blood tests,” Palak Trivedi, consultant hepatologist at the University of Birmingham, said in a statement. Seladelpar was acquired by Gilead in its $4.3 billion acquisition of CymaBay Therapeutics earlier this year. The company’s target action date with the FDA is August 14, 2024, but Ipsen’s candidate may beat Gilead to approval. Ipsen’s elafibranor, another PPAR agonist, also on Wednesday reported encouraging long-term results in a late-stage trial, as its PDUFA date approaches on June 10, 2024. The Phase III ELATIVE trial showed that at week 52, elafibranor led to “greater reductions” in the 5-D itch score and a clinically meaningful reduction in the itch domain of PBC-40, compared to placebo. The candidate also reported an improved quality of life in PBC patients, as measured by the severity of itching, sleep disturbance, and emotional impact of itching. At week 52, 58% of patients on elafibranor experienced relief from itching compared to 27% on placebo, while 80% on the treatment had no sleep disturbances. “These long-term data from the Phase III ELATIVE study further demonstrate the potential for elafibranor to provide an effective treatment option for these patients,” Sandra Silvestri, executive vice president and chief medical officer at Ipsen, said in a statement. Ipsen nabbed elafibranor in 2021 through a strategic partnership with Genfit. It paid €120 million ($130.5 million) upfront and could potentially spend up to €360 million ($391.7 million) in milestones. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Alligator Bioscience’s pancreatic cancer therapy compared favourably with standard of care chemotherapies in a recent data readout. Credit: peakSTOCK via Getty Images. Alligator Bioscience released positive data from its Phase Ib/II OPTIMIZE-1 study (NCT04888312) investigating its pancreatic cancer monoclonal antibody therapy, mitazalimab. Recommended Buyer's Guides Buyer's Guide Leading Guide to Packaging Materials, Containers and Containment Services for the Pharmaceutical Industry Buyer's Guide Top Guide for Drug Delivery Systems The Sweden-headquartered company presented the Phase II readout at the American Society of Clinical Oncology Annual Meeting (ASCO 2024), publishing the data in the Lancet Oncology on 3 June. Patients who took mitazalimab in combination with mFOLFIRINOX, demonstrated a confirmed objective response rate (ORR) of 40.4% with a median overall survival (mOS) of 14.3 months. This was an improvement compared to historical data from treatment with mFOLFIRINOX where patients typically achieve a 31.6% ORR and a mOS of 11.1 months. In an exclusive interview with Pharmaceutical Technology , Alligator CEO Dr Søren Bregenholt says: “We believe that adding three months to the overall survival is clinically meaningful. It is definitely meaningful for the patients, and it is also a differential that is approvable in almost all major territories.” Bregenholt explains that for 80% of pancreatic cancer patients, the only option available for frontline and second-line treatment is chemotherapy. He adds that approved therapies are quite “mediocre” in terms of response rate and clinical benefit. The US Food and Drug Administration (FDA) recently approved Ipsen Biopharmaceuticals’ chemotherapy combination, NALIRIFOX, for the first-line treatment of pancreatic cancer in February 2024. NALIRIFOX uses Onivyde (irinotecan liposome) with oxaliplatin, fluorouracil, and leucovorin to treat the diseases The regimen is the second US-approved Onivyde regimen for metastatic pancreatic adenocarcimoma with FOLFIRINOX receiving an approval over a decade ago. Bregenholt adds that treatment with mitazalimab has very few adverse reactions and side effects compared to the many commonly associated with the marketed chemotherapy combinations. See Also: J&J seeks expanded approvals for paediatric HIV-1 therapy FDA fast tracks Quince Therapeutics’ rare ataxia drug EryDex Mitazalimab is a CD40 agonist that treats pancreatic cancer by activating and proliferating memory T cells and enhancing the immune response. Bregenholt says that the company has begun to plan its Phase III trial for mitazalimab. “We expect to start the Phase III trial in the first half of next year,” he says.