On June 9, 2022 Forbion, a leading European life sciences venture capital firm, reported the first €470 million (USD 500 million) close of its Forbion Growth Opportunities Fund II ("Forbion Growth"), focused on investing in late-stage European life sciences companies, exceeding its €450 million target size (Press release, Forbion Capital Partners, JUN 9, 2022, View Source [SID1234615813]).

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This new Growth Opportunities Fund has attracted several new institutional investors, including pension funds PME and PMT, the Ewing Marion Kauffman Foundation and Reggeborgh, who join returning investors Pantheon, Wealth Management Partners and Eli Lilly and Company.

The second Forbion Growth Opportunities Fund will continue to invest in mostly European, later-stage biopharma companies, developing novel therapies for areas of high medical need. The Fund will target this market segment with three proven strategies: providing private growth capital for mature clinical development-stage assets, furnishing pre-IPO funding to companies pursuing a public listing in the near-term, and injecting capital and hands-on capabilities to under-valued public companies. In these financings, Forbion Growth Opportunities II aims to take leading positions with investment sizes of up to €70 million per deal. The team’s goal is to build a portfolio of 15 such investments in the most promising late-stage European life sciences companies.

Forbion expects to reach its €600 million hard cap, completing the raising of Forbion Growth Opportunities Fund II over the summer.

Sander Slootweg, Managing Partner and co-founder of Forbion said: "The European market for late stage, private life sciences investments is large and remains significantly underserved. The increase in the number of institutional investors committing to the Forbion Growth Opportunities Fund II is a testament to our successful track record in investing in late clinical stage life sciences companies. A recent example is the sale of Gyroscope Therapeutics to Novartis for a total consideration of $ 1.5 billion earlier this year, after a mere nine month hold period."

Dirk Kersten, General Partner, added: "In the past two years, we have successfully deployed Forbion Growth Opportunities Fund I, providing growth capital to a selected number of high-quality European life sciences companies. Forbion Growth has built the most experienced and sizeable team in Europe focusing on the late-stage segment, and is ready to continue investing in ambitious life sciences companies looking to accelerate their growth. We are therefore very excited to announce this substantial first close of Forbion Growth Opportunities Fund II, and look forward to the final close of the fund later this year."

On June 9, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported the company has entered into an exclusive collaboration with Pint Pharma GmbH to register and promote ORLADEYO (berotralstat) in the pan-Latin America (LATAM) region (Press release, BioCryst Pharmaceuticals, JUN 9, 2022, View Source [SID1234615812]).

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"We are pleased to join forces with Pint Pharma to bring our oral, once-daily therapy to hereditary angioedema patients in LATAM who are in need of a new treatment option. Pint Pharma is the ideal partner for BioCryst based on the team’s deep experience in rare diseases that spans multiple aspects of commercialization and their established network across this important region," said Charlie Gayer, chief commercial officer of BioCryst.

"Our partnership with BioCryst is significant for Pint Pharma given the critical unmet need among HAE patients in LATAM who are seeking an innovative treatment option for this serious disease. ORLADEYO has successfully launched in multiple markets across the globe, and we are privileged to leverage our expertise to support BioCryst in introducing this prophylactic therapy to the region," said David Munoz, chief executive officer and co-founder of Pint Pharma.

Under the terms of the agreement, Pint Pharma will be responsible for obtaining and maintaining all marketing authorizations and for commercializing ORLADEYO in the pan-LATAM region.

Pint Pharma is an Austria-based pharmaceutical company that has extensive experience developing, registering and commercializing rare disease and specialty treatments throughout Latin America and Europe.

About ORLADEYO (berotralstat)
ORLADEYO (berotralstat) is the first and only oral therapy designed specifically to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years and older. One capsule of ORLADEYO per day works to prevent HAE attacks by decreasing the activity of plasma kallikrein.

U.S. Indication and Important Safety Information

INDICATION
ORLADEYO (berotralstat) is a plasma kallikrein inhibitor indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

Limitations of use
The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for the treatment of acute HAE attacks. Additional doses or dosages of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation.

IMPORTANT SAFETY INFORMATION

An increase in QT prolongation was observed at dosages higher than the recommended 150 mg once-daily dosage and was concentration dependent.

The most common adverse reactions (≥10% and higher than placebo) in patients receiving ORLADEYO were abdominal pain, vomiting, diarrhea, back pain, and gastroesophageal reflux disease.

A reduced dosage of 110 mg taken orally once daily with food is recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) and in patients taking chronically administered P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) inhibitors (eg, cyclosporine).

Berotralstat is a substrate of P-gp and BCRP. P-gp inducers (eg, rifampin, St. John’s wort) may decrease berotralstat plasma concentration, leading to reduced efficacy of ORLADEYO. The use of P-gp inducers is not recommended with ORLADEYO.

ORLADEYO at a dose of 150 mg is a moderate inhibitor of CYP2D6 and CYP3A4. For concomitant medications with a narrow therapeutic index that are predominantly metabolized by CYP2D6 or CYP3A4, appropriate monitoring and dose titration is recommended. ORLADEYO at a dose of 300 mg is a P-gp inhibitor. Appropriate monitoring and dose titration is recommended for P-gp substrates (eg, digoxin) when coadministering with ORLADEYO.

The safety and effectiveness of ORLADEYO in pediatric patients <12 years of age have not been established.

There are insufficient data available to inform drug-related risks with ORLADEYO use in pregnancy. There are no data on the presence of berotralstat in human milk, its effects on the breastfed infant, or its effects on milk production.

On June 9, 2022 Alloy Therapeutics, a biotechnology ecosystem company, reported a collaboration and licensing agreement with Sudhir Agrawal’s Arnay Sciences to advance new RNA-based drug discovery platforms and novel chemistries spanning the fields of antisense therapeutics to immunomodulating therapeutics (Press release, Alloy Therapeutics, JUN 9, 2022, View Source [SID1234615811]). The collaboration demonstrates Alloy’s dedication to expanding its ecosystem offerings into genetic medicines. In collaboration with Dr. Agrawal, Alloy will advance the core technology platforms developed by Arnay into a multitude of new applications, which will initially be available to new companies formed within its Venture Studio, 82VS. Dr. Agrawal will also serve as the Scientific Advisory Board chair of Alloy’s genetic medicine platform technologies.

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For over three decades, Dr. Agrawal has spent his career innovating in RNA therapeutics spanning antisense and immune modulation, starting in the laboratory of the "father of antisense," Paul Zamecnik. Dr. Agrawal has published over 300 research papers and has co-authored over 400 patents worldwide, including the invention of gapmer antisense technology widely employed in antisense candidates and approved drugs. He also serves as an affiliate professor at UMass Chan Medical School, as a business advisor to Harvard Medical School’s Initiative for RNA Medicine, and is on the scientific advisory boards of Dyne Therapeutics, QurAlis, Q-State Biosciences, Lytix Biopharma, Envisagenics, HAYA Therapeutics, Bolden Therapeutics, Maze Therapeutics, the Dan Lewis Foundation for Brain Regeneration Research, and two ASO-focused 82VS companies, Aldebaran Therapeutics and Restoration Biosciences.

The licensing agreement with Arnay will enable Alloy to provide the drug discovery community non-exclusive access to RNA-based drug discovery platforms and chemistries through the successful democratization model already deployed for antibody therapeutics, through Alloy’s ATX-Gx mouse and its DeepImmune fully integrated Antibody Discovery Services. Alloy’s expansion into genetic medicines is specifically designed to meet the increased interest and momentum in the RNA therapy industry by enabling drug discovery teams to innovate efficiently through unparalleled access and generous terms.

"Working with Alloy represents an opportunity to make genetic medicines available to the widest possible community of innovators and drug developers around the globe, all thanks to Alloy’s model of democratizing access to foundational discovery tools," said Dr. Agrawal. "It has been my unique pleasure to work with Alloy, and I look forward to further advancing the new platforms with the Alloy team and leveraging their expertise in providing the community access to technology platforms. The cohesive integration of platform licensing, Discovery Services, and Venture Studios that Alloy has created will enable industry collaborators to more rapidly advance innovative therapeutics that ultimately benefit patients."

Alloy was founded in 2017 by Errik Anderson—co-founder of Adimab, Compass Therapeutics, Alector, Avitide, and Arsanis, among other companies—to minimize the intense capital requirements and timelines of biotech company formation and discovery campaigns. He recognized the need to democratize foundational platforms and tools typically made inaccessible through high-access fees and cumbersome development milestones and royalties. Through accessible licensing activities with its flagship ATX-Gx mouse, a transgenic humanized mouse that produces fully human antibodies, the company has amassed more than 130 partnerships across academia, biotech, and large biopharma. It continues to expand its technology portfolio and service offering to support a broader range of drug discovery and development teams.

"We have seen the impact of disruptive access in our antibody discovery offering and are thrilled to build upon this model to serve developers of genetic medicines better," says Errik Anderson, Alloy CEO and founder. "We were delighted to learn a seminal figure in genetic medicine therapies like Sudhir was aligned with our mission to democratize enabling, pre-competitive technologies. We look forward to seeing the therapeutic innovation this collaboration spurs across the global scientific community."

Dr. Agrawal has leveraged his decades of experience to develop novel chemistries and structures for RNA therapeutics. These breakthrough platforms are designed to address limitations of currently used chemistries, such as specificity, off-target effects, delivery, and unintended inflammatory responses. Dr. Agrawal’s RNA-based drug discovery platforms have broad applications in developing antisense therapeutics by targeting RNA, including mRNA, pre-mRNA, microRNA, and ncRNA, and for immune-modulation therapeutics. These platforms strengthen Alloy’s ability to help its partners address a vast range of drug discovery challenges in creating genetic medicines. Alloy intends to provide broad access to these technologies and platforms as part of their larger Innovation Subscription offerings and through individual, non-exclusive licensing activities. Initially, the new genetic medicines platforms and services will be exclusively available through company collaborations within 82VS portfolio companies.

"Our Venture Studio model facilitates Alloy’s expansion of new modalities by enabling our portfolio companies to access and de-risk new technologies, yet not be beholden to using an unproven approach," said Dr. Chris Pacheco, General Partner at 82VS. "This work provides our 82VS portfolio companies the upside of accessing new, cutting-edge technologies at the earliest stage of the company development. This access is unprecedented in the industry and gives our companies a significant advantage in developing the best medicines. Inside the ecosystem, we have created win-win scenarios for Alloy, 82VS companies, technology developers, and, in the end, patients. And isn’t that what we are all trying to do in the end?"

Arnay has pending patent applications claiming these technologies. Alloy has gained exclusive rights to these patents for internal use and for sublicensing. Under the licensing agreement, Alloy will pay an upfront fee and will share sublicensing income with Arnay.

On June 9, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing therapies that combine both targeted and immune-mediated mechanisms, reported that key takeaways from the TPST-1120 clinical program provided by Mark Yarchoan, M.D., associate professor of oncology at Johns Hopkins School of Medicine, at its June 5th investor event held in connection with the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, Tempest Therapeutics, JUN 9, 2022, View Source [SID1234615808]). The company also revised its cash guidance. Dr. Yarchoan also presented the TPST-1120 Phase 1 results in an oral presentation at ASCO (Free ASCO Whitepaper) on Tuesday, June 7.

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Dr. Yarchoan reviewed and discussed TPST-1120 results both as a single agent and in combination with nivolumab in a webcast presentation that is available on the Tempest website at View Source His conclusions include:

The monotherapy arm consisted of one of the more challenging groups of tumors to treat in a Phase 1 trial, e.g., dominated by patients with late-line pancreatic and cholangiocarcinoma (CCA), where he considered stable disease a "win."
A number of patients in the monotherapy arm had meaningfully-prolonged stable disease, showing that TPST-1120 has activity as a monotherapy
Two patients with IDH1 mutated CCA, a mutation found in ~15-30% of intrahepatic CCA, had stable disease extending out to five and ten months, respectively, vs. less than three months for historical standard-of-care values, indicating that an IDH1 mutation is a potential biomarker for patient sensitivity to TPST-1120
In the combination arm, two patients with renal cell carcinoma (RCC) and one with metastatic CCA achieved partial response when treated with the higher doses of TPST-1120 in combination with pembrolizumab
Both RCC patients had progressed on prior anti-PD1 therapy, providing strong evidence that TPST-1120 overcomes resistance to anti-PD1 therapy
The patient with metastatic CCA had received multiple lines of prior systemic therapy and was PDL1-negative, mismatch repair proficient, and had a TMB of less than 10 mutations per megabase, supporting that TPST-1120 can reprogram the TME in immune-resistant type cancers
TPST-1120 Monotherapy Results

In the monotherapy portion of the trial, 19 evaluable patients with late-line treatment-refractory solid tumors, including pancreatic, cholangiocarcinoma, and colorectal cancers, were treated with oral twice-daily TPST-1120. The results showed that 53% (10/19) of patients experienced clinical benefit in the form of disease control, including tumor shrinkage in 21% of the patients. Two patients with late-line CCA, an aggressive tumor type and disease setting usually unresponsive to therapy, including IO therapies, achieved durable stable disease and one of the patients achieved durable tumor shrinkage.

TPST-1120 and Nivolumab Combination Therapy Results

In the combination therapy portion of the trial, 15 evaluable patients with heavily-pretreated renal cell carcinoma, hepatocellular carcinoma (HCC) and CCA were treated with oral twice-daily TPST-1120 and the anti-PD-1 therapy, nivolumab. All of the HCC and RCC patients had received an approved anti-PD-1 therapy in at least one prior line of therapy and discontinued that treatment due to disease progression. Promising objective responses (RECIST v1.1) were observed in two patients with late-line RCC who had previously progressed on anti-PD-1 therapy without an objective response (ORR 50%, n=2/4, in evaluable RCC patients). A third RECIST response was observed in a patient with late-line, heavily pre-treated CCA, a tumor type generally not responsive to anti-PD-1 alone.

Notably, all three responders were treated at the two highest doses of TPST-1120 (ORR 30%, 3/10).

Safety

TPST-1120 was well tolerated as both a monotherapy and in combination with nivolumab. The majority of the treatment-related adverse events were Grade 1 and 2, and included nausea, fatigue and diarrhea. No dose-limiting toxicities were reported during dose escalation.

Financial Update

Following the $15 million private investment in public equity financing completed in April 2022, Tempest’s cash and cash equivalents are currently expected to be sufficient to fund its current operating plans into the first quarter of 2024.

About TPST-1120

TPST-1120 is a first-in-class1 oral selective PPAR⍺ antagonist with a dual mechanism designed to target both tumor cells directly and suppressive immune cells in the tumor microenvironment. Both types of targeted cells are dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy and in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In addition to the study presented at ASCO (Free ASCO Whitepaper), in collaboration with F. Hoffmann La Roche, TPST-1120 is also advancing through a randomized, first-line, global, Phase 1b/2 clinical study in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic hepatocellular carcinoma.

On June 9, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported updates on its Phase 1 clinical trial evaluating FPI-1434 as a monotherapy for the treatment of solid tumors expressing IGF-1R and its Phase 1 clinical trial evaluating FPI-1966 for the treatment of solid tumors expressing FGFR3 (Press release, Fusion Pharmaceuticals, JUN 9, 2022, View Source [SID1234615807]). In the FPI-1434 trial, the Company now expects to report Phase 1 safety, pharmacokinetics, and imaging data, including any evidence of anti-tumor activity, and details on the dosing regimen, in the first half of 2023, rather than in the second half of 2022. Fusion is also updating guidance for FPI-1966 and expects to dose the first patient in this study in the second half of 2022, rather than in the second quarter of 2022.

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"Fusion is pioneering the development of next-generation, alpha-emitting radiopharmaceuticals, and we are working to identify the most effective dosing regimen that maximizes the therapeutic window in new these treatment paradigms," said Fusion Chief Executive Officer John Valliant, Ph.D. "To this end, we are evaluating two potential dosing regimens in our FPI-1434. Initial data from a sub-study of the "cold antibody" dosing regimen, to be presented in full next week at the Society of Nuclear Medicine and Medical Imaging (SNMMI) annual meeting, showed encouraging early results of the ability to maximize the therapeutic window and drive higher doses into the tumor. Following the protocol amendment to incorporate the cold antibody study arm, sites have been slow to initiate and, as a result, patient enrollment in this portion of the study is now lagging our prior forecasts, delaying the availability of the data from our original expectations. While our timelines are extended, we believe it is important to pursue optimization of this cold antibody dosing regimen and we look forward to presenting the full dataset in the first half of 2023.

Dr. Valliant continued: "We’ve experienced similar study site startup challenges in our Phase 1 trial of FPI-1966. As a result, we are updating guidance for timing of the first patient to be dosed, and now expect it to occur in the second half of this year. Delays are resulting from what we believe is a combination of staffing/resourcing shortages and administrative complications with various review boards for radiopharmaceuticals at the trial sites, and we have mitigation plans in place to address them. Importantly, our conviction in these programs and investigator enthusiasm remains strong, particularly given our pursuit of cancer types with high unmet medical need."

Overview of FPI-1434 Phase 1 Clinical Trial

In the Phase 1 study, Fusion is exploring various dosing levels of FPI-1434 as well as two dosing regimens: one with FPI-1434 alone, and another in which a small dose of cold antibody (naked IGF-1R antibody without the isotope) is administered prior to each dose of FPI-1434.
Data observed from a completed cold-antibody sub-study demonstrate the potential of pre-dosing cold antibody prior to FPI-1434 to increase the tumor to non-tumor distribution ratio of the radiopharmaceutical and thereby potentially improve the therapeutic window. As a result, Fusion initiated the dosing regimen evaluating pre-administration of cold antibody prior to FPI-1434 following a protocol amendment to the ongoing Phase 1 study of FPI-1434. Fusion expects to present more detailed data from the cold-antibody sub-study at the Society of Nuclear Medicine and Medical Imaging (SNMMI) 2022 Annual Meeting taking place in Vancouver, British Columbia from June 11-14, 2022.
Given the protocol amendment to include the dosing regimen evaluating pre-administration of cold-antibody and the time required to generate sufficient data to be able to provide information on both dosing paradigms, as well as ongoing enrollment challenges relating to staffing and resourcing issues at trial sites, and additional review boards required at trial sites for novel alpha-emitting radiopharmaceuticals, Fusion now expects to report Phase 1 safety, pharmacokinetics, and imaging data, including any evidence of anti-tumor activity, and details on the dosing regimen, in the first half of 2023.
Overview of FPI-1966 Phase 1 Clinical Trial

The Phase 1, non-randomized, open-label clinical trial of FPI-1966 in patients with solid tumors expressing FGFR3, intended to investigate safety, tolerability and pharmacokinetics and to establish the recommended Phase 2 dose, has been initiated.
The first cohort in this study will comprise four sub-groups in which various doses of non-radiolabeled vofatamab (cold antibody) will be evaluated to assess the impact of pre-dosing on tumor uptake.
As previously disclosed, Fusion experienced initial challenges with study site initiations and is further experiencing enrollment challenges similar to the FPI-1434 study, including study backlogs as COVID-19 headwinds ease, staffing shortages at trial sites, and additional review boards required at trial sites for novel alpha-emitting radiopharmaceuticals. As a result, Fusion now expects to dose the first patient in the FPI-1966 Phase 1 study in the second half of 2022. In addition, Fusion plans to provide updated guidance for preliminary pharmacokinetic, imaging and safety data from the first patient cohort once patient enrollment begins.
About FPI-1434
FPI-1434 is a radioimmunoconjugate designed to target and deliver alpha emitting medical isotopes to cancer cells expressing IGF-1R, a receptor that is overexpressed on many tumor types. FPI-1434 utilizes Fusion’s Fast-Clear linker to connect a human monoclonal antibody that targets IGF-1R with actinium-225, a powerful alpha-emitting isotope with desirable half-life and decay chain properties.

About FPI-1966
FPI-1966 is a targeted alpha therapy designed to target and deliver an alpha emitting medical isotope, actinium-225, to cancer cells expressing FGFR3; a receptor that is overexpressed on several tumor types, including head and neck and bladder cancers. FPI-1966 utilizes Fusion’s Fast-Clear linker to connect vofatamab, the human monoclonal antibody that targets FGFR3, with actinium-225. Vofatamab was previously evaluated as a therapeutic agent in a Phase 1b/2 trial and was reportedly well-tolerated.