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Catalent Signs Commercial Supply Agreement with Phathom Pharmaceuticals

On September 16, 2021 Catalent, the leading global provider of development sciences and manufacturing platforms for medicines, including biotherapeutics; cell and gene therapies; and consumer health products, reported that it had signed a commercial supply agreement with Phathom Pharmaceuticals, a late clinical-stage biopharmaceutical company focused on developing and commercializing novel treatments for gastrointestinal diseases, for its lead compound, vonoprazan, which is a novel, orally active-potassium competitive acid blocker (P-CAB) (Press release, Catalent, SEP 16, 2021, https://www.catalent.com/catalent-news/catalent-signs-commercial-supply-agreement-with-phathom-pharmaceuticals/ [SID1234587825]).

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P-CABs are a new class of medicines that block acid secretion in the stomach. Vonoprazan is currently in late clinical-stage development for the treatment of gastric acid-related diseases and disorders, including gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) bacterial infection. Phathom has the rights for the development and commercialization of vonoprazan in the U.S., Europe, and Canada.

Under the terms of the agreement, should the drug receive FDA approval, Catalent will undertake the commercial manufacturing and packaging of the product at its large-scale oral solid dose manufacturing site in Winchester, Kentucky.

"As Phathom readies for the potential approval and launch of our first product, we are pleased to have secured Catalent as a strategic partner to support our vonoprazan commercial manufacturing and packaging capabilities," said Azmi Nabulsi, M.D., Chief Operating Officer of Phathom Pharmaceuticals. "This agreement further provides us with scalable commercialization resources and brings us closer to delivering on our commitment to change the treatment landscape for acid-related gastrointestinal diseases."

"This agreement is the start of long-term partnership between Catalent and Phathom, and we are pleased to be able to be part of a program that aligns with our ‘patient first’ philosophy, as this drug offers a true innovation for patients," commented Dr. Aris Gennadios, President, Softgel & Oral Technologies, Catalent. "Our Winchester facility has an extensive history of manufacturing and robust track record in supporting product launches, and has all the experience and capabilities, particularly related to fluid bed technologies, to meet the needs of this program as it nears commercialization."

Opened in 1992, Catalent’s Winchester facility has evolved into one of the industry’s premier sites for complex oral drug formulation and manufacturing. The site has launched more than 100 new products into the market since its inception and produces over three-billion tablets and capsules annually. The site doubled its footprint to 180,000 square feet in 2015, and in 2019 undertook a $40 million investment that saw the installation of new equipment to increase its tablet and capsule manufacturing capabilities, including laser drill for osmotic drug delivery, stick pack dosage manufacturing, integrated packaging lines, and expanded roller compaction and fluid bed capacity.

Monopar Initiates Open-Label Phase 1b Clinical Trial Evaluating Camsirubicin in Patients with Advanced Soft Tissue Sarcoma

On September 16, 2021 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported its Phase 1b open-label dose-escalation clinical trial of camsirubicin in the US is active and recruiting patients (Press release, Monopar Therapeutics, SEP 16, 2021, View Source [SID1234587824]). The trial is evaluating the safety and anti-tumor activity of increasing doses of camsirubicin in combination with growth factor support (pegfilgrastim/G-CSF) for the treatment of advanced soft tissue sarcoma (ASTS).

"This trial initiation marks a pivotal moment in the development of camsirubicin. The goal is to determine whether escalating doses of camsirubicin result in an increased anti-cancer effect in patients with ASTS, while also maintaining an appropriate safety profile," said Chandler Robinson, MD, Monopar’s Chief Executive Officer.

"We are very pleased with the positive response and dedication from physicians and clinical sites interested in participating in this clinical trial, enabling us to initiate the study in the US faster than we anticipated," said Octavio Costa, MD, Monopar’s Chief Medical Officer.

Currently, ASTS patients receive doxorubicin, a widely used cancer drug that becomes more effective in higher doses. Unfortunately, patients are forced to stop treatment once a cumulative lifetime dose limit is reached, as higher dosing causes severe irreversible heart damage.

"Camsirubicin has already shown anti-tumor activity comparable to doxorubicin in a pilot study in ASTS patients, without any signs of irreversible heart damage," said Andrew Mazar, PhD, Monopar’s Chief Scientific Officer. "We are excited, as the previous study’s dose of camsirubicin will be the first dose level in this Phase 1b clinical trial. From there the dose will increase, hopefully with corresponding increases in anti-cancer effect, to identify a recommended Phase 2 dose (RP2D) of camsirubicin when given with concomitant pegfilgrastim."

Further information about the camsirubicin trial is available at www.ClinicalTrials.gov under study identifier NCT 05043649.

About Camsirubicin

Camsirubicin is a novel proprietary analog of the widely used cancer drug doxorubicin. It has been investigated in ASTS patients in a Phase 1 and a single arm Phase 2 clinical trial. In these studies, no camsirubicin-treated patients developed the irreversible cardiotoxicity common to doxorubicin at higher cumulative doses. The most frequent adverse event observed in the Phase 1 study was neutropenia, which was mitigated in the Phase 2 study through the use of prophylactic G-CSF. Based on encouraging clinical results to date, the Phase 1b trial is designed to test camsirubicin at even higher doses than previously administered while using concomitant prophylactic G-CSF to prevent neutropenia.

About Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are a diverse type of cancer that typically develop in the connective tissue of the body. According to the American Cancer Society, in 2021, an estimated 13,460 new STS cases will be diagnosed in the US alone, and about 5,350 people will not survive their disease. These tend to be the advanced cases; those with sarcomas that are unresectable and/or have metastasized. The average life expectancy from time of diagnosis for those patients with advanced disease (ASTS) is about 12 to 15 months. Doxorubicin is the current standard of care in the 1st-line setting for ASTS, and has been for decades, since there have been no 1st-line therapeutic advancements that have improved overall survival for this patient population.

NuCana Announces Four Poster Presentations at the ESMO Congress 2021

On September 16, 2021 NuCana plc (NASDAQ: NCNA), reported the presentation of four posters at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (Press release, Nucana BioPharmaceuticals, SEP 16, 2021, View Source [SID1234587823]). The Company presented additional data from the ongoing Phase 1b/2 study of NUC-3373 in combination with standard therapies in patients with advanced colorectal cancer (NuTide:302), final data from the Phase 1 study of NUC-3373 in patients with advanced solid tumors (NuTide:301), and additional interim data from the Phase 1 study of NUC-7738 in patients with advanced solid tumors. The Company also presented a trials-in-progress poster describing the ongoing Phase 3 study of Acelarin plus cisplatin in patients with advanced biliary tract cancer.

"The posters being presented during ESMO (Free ESMO Whitepaper) continue to support the potential of our ProTide platform to transform both existing as well as novel nucleoside analogues into more effective and safer medicines for patients with cancer," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "Looking ahead to the remainder of 2021 and first half of 2022, we have multiple milestones that we plan to announce. These include announcing the outcome of the first interim analysis in the Phase 3 NuTide:121 study of Acelarin plus cisplatin in patients with biliary tract cancer, initiating a registrational study for NUC-3373 in patients with colorectal cancer, and initiating and announcing data from a Phase 2 study of NUC-7738 in patients with advanced solid tumors."

Details of NuCana’s e-poster presentations during the ESMO (Free ESMO Whitepaper) Congress 2021 being held September 16-21, 2021 are as follows:

NUC-3373

NuCana presented two posters on NUC-3373, its ProTide transformation of the active anti-cancer metabolite of 5-fluorouracil (5-FU), one of the most widely used anti-cancer medicines. NUC-3373 has been designed to overcome the main challenges associated with 5-FU, including cancer-resistance mechanisms, the generation of toxic metabolites and unfavorable pharmacokinetics.

Poster Title: A Phase Ib study of NUC-3373, a targeted inhibitor of thymidylate synthase, in combination with standard therapies in patients with advanced colorectal cancer (NuTide:302)

This poster describes encouraging interim data from 38 patients with metastatic colorectal cancer. In this difficult-to-treat group, with patients having received a median of four prior lines of therapy, NUC-3373, with or without leucovorin, demonstrated encouraging signs of efficacy. In addition to several patients achieving a longer progression-free survival on NUC-3373 than they had on their prior therapy, tumor reductions were observed in three patients: one who experienced a 40% reduction in their target lesion and two others with 28% and 15% reductions, respectively, in overall tumor burden. NUC-3373 also demonstrated a favorable safety profile in this patient population with no FBAL or FUTP-associated Grade 3 or 4 toxicities, such as hand-foot syndrome, diarrhea or neutropenia.

Based on these encouraging interim results, NuTide:302 has been expanded to a Phase 1b/2 study and now allows enrollment of less heavily pre-treated patients, including second-line colorectal cancer patients. A registrational study of NUC-3373 in second-line colorectal cancer patients is also planned.

Poster Title: Final results of a first-in-human study of the ProTide thymidylate synthase inhibitor NUC-3373, in patients with advanced solid tumours (NuTide:301)

This poster highlights final results from the NuTide:301 study in patients with advanced solid tumors. NUC-3373 showed a favorable safety profile and encouraging anti-cancer activity, including in patients previously treated with 5-FU. Additionally, three patients achieved stable disease lasting at least 9 months. NUC-3373 demonstrated an attractive pharmacokinetic profile with a long plasma half-life of between 6 and 14 hours compared to 8 to 14 minutes for 5-FU. Furthermore, NUC-3373 generated approximately 300 times higher levels of the active anti-cancer metabolite, FUDR-MP, than 5-FU. The recommended Phase 2 monotherapy dose of NUC-3373 was established at 2,500mg/m2.

NUC-7738

NUC-7738, a ProTide transformation of a novel anti-cancer nucleoside analog, 3’-deoxyadenosine, has multiple potential anti-cancer mechanisms of action and is being evaluated in a Phase 1 study in patients with advanced solid tumors who have exhausted all standard therapies.

Poster Title: A first-in-human study of NUC-7738, a ProTide transformation of 3’-deoxyadenosine, in patients with advanced solid tumors (NuTide:701)

This poster describes interim data from the ongoing Phase 1 study (NuTide:701) and the data demonstrate NUC-7738’s encouraging anti-cancer activity in multiple tumor-types. NUC-7738 has been well tolerated with no Grade 3 or 4 treatment-related adverse events and no dose-limiting toxicities. The ProTide generated high levels of the key anti-cancer metabolite, 3’-dATP, which had a prolonged intracellular half-life and was still detectable after 50 hours.

Three case studies were described detailing two patients with metastatic melanoma and one patient with metastatic lung adenocarcinoma who achieved reductions in the size of target lesions coupled with prolonged stable disease. Following treatment with NUC-7738, one patient with metastatic melanoma became eligible for surgery and their tumor was completely resected.

Recruitment to the NuTide:701 study is ongoing and once the recommended Phase 2 dose has been established, NUC-7738 is expected to advance into the Phase 2 part of the study.

Acelarin

Poster Title: Phase III study of NUC-1031 + cisplatin vs gemcitabine + cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121)

This trial-in-progress poster highlights the Company’s global multi-center, randomized Phase 3 study comparing Acelarin, a ProTide transformation of gemcitabine, in combination with cisplatin, to gemcitabine in combination with cisplatin in up to 828 patients with advanced biliary tract cancer who have not previously received treatment for advanced disease. Enrollment of 418 evaluable patients has been achieved and the first of three interim analyses is expected to occur in the first half of 2022. NuCana believes that a statistically significant improvement in the Objective Response Rate (ORR) at the first interim analysis, accompanied by positive trends in other endpoints, has the potential to allow for accelerated approval of a new drug application (NDA) for Acelarin in the United States.

Abstracts and full session details can be found at www.esmo.org

clinical-collaboration-with-Amgen

On September 16, 2021 Boehringer Ingelheim reported a clinical phase I collaboration with Amgen to evaluate the combination of BI 1701963, the first and most advanced SOS1::pan-KRAS inhibitor exhibiting activity against a broad spectrum of KRAS alleles, and LUMAKRAS (sotorasib), the first US Food and Drug Administration (FDA) approved KRASG12C inhibitor for adult patients with locally advanced or metastatic non-small cell lung cancer (Press release, Boehringer Ingelheim, SEP 16, 2021, View Source [SID1234587821]). The trial will investigate potential synergistic effects of this combination, possibly improving therapeutic outcomes beyond those of KRASG12C inhibitor therapy alone, specifically for people living with lung and colorectal cancers.

Preclinical data suggest that the combination of a KRASG12C inhibitor with a SOS1::pan-KRAS inhibitor may result in increased anti-tumor activity in KRAS G12C-driven cancers based on the complementary mechanisms of these targeted oncology agents.1,2 By shifting the equilibrium from active KRAS towards the inactive form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C-mutant tumors to covalent KRASG12C inhibitors that bind to inactive KRAS. In addition, SOS1 inhibitors block feedback reactivation which occurs upon pathway inhibition.

"We are excited to partner with Amgen, who have pioneered KRAS G12C inhibition, and to further expand our program to make a difference for people living with KRAS-driven cancers," said Francesco Di Marco, Ph.D., Corporate Senior Vice President, Global Therapy Area Head Oncology at Boehringer Ingelheim. "Boehringer Ingelheim follows an ‘all-in’ research approach to taking cancer on, including the first and most advanced SOS1::pan-KRAS inhibitor which we investigate in several combinations and cancer types to realize even more opportunities to deliver potential therapeutic benefits to cancer patients."

Under the terms of the non-exclusive collaboration, Amgen will be the sponsor of the trial and Boehringer Ingelheim and Amgen will jointly share the costs of and oversee clinical development for the combined therapy.

About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that binds to the catalytic domain of SOS1 preventing the interaction with inactive KRAS. This reduces the formation of active KRAS and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. SOS1 inhibition also simultaneously blocks feedback driven reactivation of the MAPK pathway. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR) (Free AACR Whitepaper). BI 1701963 is currently being evaluated in phase I clinical trials in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors, KRASG12C inhibitors or irinotecan.

Herantis Pharma Plc: 1,346,500 new shares registered with the trade register

On September 16, 2021 Herantis Pharma Plc ("Herantis" or the "Company"), an innovative drug development company pioneering new disease modifying and regenerative biologic and gene therapies, reported on 15 September 2021 the result of the offering of new shares (the "Placing Shares") in a private placement to institutional and other qualified investors (the "Placing") (Press release, Herantis Pharma, SEP 16, 2021, View Source;1-346-500-new-shares-registered-with-the-trade-register,c3416563 [SID1234587820]). In the Placing, the Company issued a total of 1,346,500 Placing Shares. The Placing Shares have today been registered with the trade register maintained by the Finnish Patent and Registration Office.

Following the registration of the Placing Shares, the total number of registered shares in the Company is 11,103,568. The Placing Shares will be issued in the book-entry system (ISIN code FI4000087861) on or about 20 September 2021. After this, and registration on the investors’ book-entry accounts, they will confer shareholder rights in the Company. The Placing Shares are expected to be ready for delivery to the investors against payment through Euroclear Finland Ltd or, as applicable, through Euroclear Sweden AB on or about 20 September 2021.

Trading in the Placing Shares is expected to commence on Nasdaq First North Growth Market Finland and Nasdaq First North Growth Market Sweden on or about 20 September 2021.