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Fusion Pharmaceuticals Announces Third Quarter 2021 Financial Results and Clinical Program Update

On November 9, 2021 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported financial results for the third quarter ended September 30, 2021 and provided an update on clinical and corporate developments (Press release, Fusion Pharmaceuticals, NOV 9, 2021, View Source [SID1234594931]).

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Clinical Update

FPI-1434

Fusion now expects to provide multi-dose safety and imaging data, and recommended Phase 2 dose, in the second half of 2022 rather than in the first half of 2022. The shift in timelines is primarily associated with a decrease in patient enrollment rates attributable to the impact of the COVID-19 pandemic.

Chief Executive Officer John Valliant, Ph.D. commented, "Despite our efforts to mitigate the impacts of the COVID-19 pandemic, including the addition of new trial sites in multiple geographic regions, we have seen patient enrollment rates decline largely due to resourcing and reduced staffing issues at trial sites. Longer timelines to enroll patients have persisted and therefore we are shifting our expectation for multi-dose data to the second half of 2022. We continue to make patient recruitment a top priority, are working closely with our trial sites to support their efforts and believe that with increased vaccination rates recruitment will return to previous levels."

Fusion continues to anticipate the initiation of a Phase 1 combination study with FPI-1434 and KEYTRUDA (pembrolizumab) to occur six to nine months following determination of the recommended Phase 2 dose of FPI-1434 monotherapy. In addition, the study arm exploring the impact on biodistribution and tumor uptake of administration of a dose of naked ("cold") IGF-1R antibody prior to each dose of FPI-1434 is ongoing.

Dr. Valliant continued, "Although the Phase 1 study of FPI-1434 is experiencing delays during these unprecedented times, we continue to believe in the significant opportunity we have to address a broad array of tumor types with high unmet need and we are working diligently to optimize the development program and progress the study for the benefit of patients."

FPI-1966

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 with the first study site open to recruitment. Fusion expects to dose the first patient in the first quarter of 2022 and expects interim data from the first patient cohort in the first quarter of 2023.

FPI-2059

FPI-2059 is a small molecule radioconjugate in development as a targeted alpha therapy for various solid tumors. The molecule targets neurotensin receptor 1 (NTSR1), a promising target for cancer treatment, that is overexpressed in multiple solid tumors. FPI-2059 combines Ipsen’s IPN-1087, which Fusion acquired in 2021, with actinium-225. Fusion continues to anticipate submitting an IND application for FPI-2059 in the first half of 2022.

Study Shows Biocept’s Switch-Blocker Technology Enhances Performance of Conventional PCR-Based Liquid Biopsy Assays in Detecting Rare Cancer Mutations

On November 9, 2021 Biocept, Inc. (Nasdaq: BIOC), a leading provider of molecular diagnostic assays, products and services, reported the publication of a study showing that the addition of Switch-Blocker technology to common PCR-based liquid biopsy assays significantly increased sensitivity in detecting rare cancer mutations (Press release, Biocept, NOV 9, 2021, View Source [SID1234594947]). The abstract was published in the November 2021 issue of the Journal of Molecular Diagnostics.

Biocept’s proprietary Switch-Blocker technology enriches oncogenic mutations of interest while suppressing wild-type (normal) DNA, resulting in ultra-high sensitivity, specificity and accuracy. In this study, Switch-Blockers were combined with conventional real-time PCR and droplet digital PCR (ddPCR) assays.

"Our quantitative Switch-Blocker technology demonstrates an unprecedented ability to find and distinguish extremely rare genetic events—even in blood that contains mostly DNA from normal white blood cells," said Michael Dugan, Chief Medical Officer and Medical Director of Biocept. "This can greatly enhance the clinical sensitivity of our cell-free tumor DNA assays and has broad application in the continued development of highly sensitive and quantitative molecular diagnostic assays used to evaluate cerebrospinal fluid or blood from patients with cancer. Switch-Blocker-based assays can help detect cancer biomarkers that otherwise might be missed, improving treatment selection. They can also be used to evaluate treatment-related changes, find minimal residual disease or identify early disease recurrence."

Results showed that the addition of Switch-Blockers increased the sensitivity of allele-specific primer assays by more than 200 times, from about 1% minor allele frequency (MAF) to better than 0.01%. The sensitivity of multiplex competitive allele-specific TaqMan assays, commonly used with PCR amplification, were increased greater than 1,000 times, from about 10% MAF to 0.01% or better. The ability to significantly increase the sensitivity of conventional mutation assays using Switch-Blocker technology is critical for helping to find rare genetic events in a wide range of applications, including solid tumor cancers, where a majority of biomarkers in blood occur at less than 1% MAF.

The abstract (#TT33), titled "The Use of Switch-Blocker Probes for the Ultra-High Sensitivity of Detection of Rare Genetic Events Using Conventional Real-Time and Droplet Digital PCR Assays," can be accessed here.

About Switch-Blocker Technology

Biocept’s proprietary Switch-Blocker platform is the basis for the company’s Target Selector assays and can be used with tissue, blood and cerebrospinal fluid (CSF) samples. The technology enables industry-leading sensitivity for the detection of mutations/variants from circulating tumor DNA (ctDNA). It has been validated to 0.05% minor allele frequency in blood, which provides significant advantages for identifying actionable cancer biomarkers and assessing therapeutic tumor response. Switch-Blockers enhance the performance and specificity of the PCR method, the most widely used amplification approach for clinical diagnostic applications and can be customized to aid in biopharmaceutical research for the development of targeted therapies for cancer. Switch-Blocker technology also has been validated and found to be highly sensitive, quantitative and reproducible in detecting the presence of the SARS-CoV-2 virus that causes COVID-19 infections.

Ascendis Pharma A/S Presents New Non-Clinical Data for TransCon™ TLR7/8 Agonist Oncology Program at SITC 2021

On November 9, 2021 Ascendis Pharma A/S (Nasdaq: ASND) reported two poster presentations featuring new non-clinical data for its investigational TransCon TLR7/8 Agonist product candidate at SITC (Free SITC Whitepaper) 2021, the annual meeting for the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place virtually and in person November 10-14 in Washington, D.C (Press release, Ascendis Pharma, NOV 9, 2021, View Source [SID1234594982]).

The data show that, as designed, TransCon TLR7/8 Agonist, which leverages the Company’s innovative TransCon hydrogel technology, provides sustained activation of both innate and adaptive immune mechanisms with low systemic cytokine levels.

The posters being presented at SITC (Free SITC Whitepaper) 2021 are:

Poster #769
Friday,
November 12 A Single Dose of Intratumoral TransCon TLR7/8 Agonist Monotherapy Promoted Sustained Activation of Antigen Presenting Cells Resulting in CD4+ and CD8+
T Cell Activation and Tumor Growth Inhibition
Poster #16
Saturday,
November 13
Tumor Growth Inhibition Mediated by a Single Dose of Intratumoral TransCon TLR7/8 Agonist Associated with Activated Circulating T and B cells and Sustained Low Levels of Systemic Cytokines

"We are designing TransCon TLR7/8 Agonist for sustained and controlled release of resiquimod, a potent TLR7/8 agonist, with the goal of maximizing therapeutic benefit and addressing the known limitations of current approaches, including serious systemic toxicity and rapid effusion from the tumor," said Juha Punnonen, Ascendis Pharma’s Senior Vice President and Head of Oncology. "We are incredibly pleased to confirm with these non-clinical studies that a single intratumoral injection of sustained release unmodified resiquimod delivered through our unique hydrogel technology worked in the expected way. We look forward to sharing initial data from our Phase 1/2 clinical trial soon."

About TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist is an investigational long-acting prodrug of resiquimod, a small molecule agonist of Toll-like receptors (TLR) 7 and 8 designed to provide sustained activation of intratumoral antigen-presenting cells driving tumor antigen presentation and induction of immune stimulatory cytokines for weeks or months with a single intratumoral injection.

Ascendis Pharma is currently conducting a Phase 1/2 study, called the transcendIT-101 Study (ClinicalTrials.gov Identifier: NCT04799054), to evaluate TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab in dose escalation and dose expansion cohorts. The primary objectives are to evaluate safety and tolerability and to define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab.

Acorda Therapeutics Announces Agreement to Commercialize INBRIJA® in Germany

On November 9, 2021 Acorda Therapeutics, Inc. (Nasdaq: ACOR) reported that it has entered into distribution and supply agreements with Esteve Pharmaceuticals GmbH (ESTEVE) to commercialize INBRIJA 33 mg (levodopa inhalation powder, hard capsules) in Germany (Press release, Acorda Therapeutics, NOV 9, 2021, View Source [SID1234595034]). INBRIJA is indicated in the EU for the intermittent treatment of episodic motor fluctuations (OFF episodes) in adult patients with Parkinson’s disease treated with a levodopa/dopa-decarboxylase inhibitor. (1) Acorda had previously announced an agreement with ESTEVE to commercialize INBRIJA in Spain.

"We are delighted to announce this second commercialization agreement with ESTEVE, which will make INBRIJA available to the many people with Parkinson’s in Germany who would benefit from an "as needed" treatment for their OFF periods," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "ESTEVE has an impressive track record of successfully commercializing pharmaceuticals in Europe for neurological and other indications. We continue to be in active discussions with additional companies for the rights to distribute INBRIJA in other countries in Europe and the rest of the world."

Under the terms of the distribution agreement, ACORDA will receive a €5 million upfront payment, and will receive additional sales-based milestones. ACORDA will also receive a significant double-digit percent of the selling price of INBRIJA in Germany in exchange for supply of the product. ESTEVE will have the exclusive distribution rights to INBRIJA in Germany and ACORDA will supply the product to ESTEVE. ESTEVE expects to launch INBRIJA in Germany by mid-2022.

According to current population estimates, there are up to 400,000 people living with Parkinson’s disease in Germany, and there are 20 new cases per 10,000 people per year. (2)

Shattuck Labs Reports Third Quarter 2021 Financial Results and Recent Business Highlights

On November 9, 2021 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease with three ongoing Phase 1 clinical trials, reported financial results for the third quarter ended September 30, 2021, and provided recent business highlights (Press release, Shattuck Labs, NOV 9, 2021, View Source [SID1234594797]).

"We designed the ARC platform to simultaneously block immune checkpoint targets and activate immune costimulatory receptors in the TNF superfamily. The clinical data presented this week at SITC (Free SITC Whitepaper) demonstrate evidence of anti-tumor activity, target receptor binding, and dose-dependent immune activation specific to each of CD40 and OX40," said Taylor Schreiber, M.D., Ph.D., and Chief Executive Officer of Shattuck. "Both compounds have been well tolerated and are demonstrating predictable dose-response relationships in humans. The doses we have explored to date remain below the recommended Phase 2 doses of benchmark CD47 inhibitors and PD-L1 inhibitors, and we look forward to continuing dose escalation of both SL-172154 and SL-279252 into dose levels that we believe will maximize the pharmacodynamic activity and anti-tumor activity of each compound."

"We are very encouraged by the initial data from the Phase 1 trial of SL-172154. The data show an excellent safety profile, high CD47 receptor occupancy and clear evidence of CD40 engagement, which collectively differentiate SL-172154 from other CD47 inhibitors," said Nehal Lakhani, M.D., Ph.D., South Texas Accelerated Research Therapeutics (START) Midwest, Grand Rapids, MI. "We desperately need new therapies for late-stage ovarian cancer patients, particularly in the platinum resistant setting. The combined actions of CD47 inhibition and CD40 activation provided by SL-172154 represents a strategy that has not yet been examined in this disease and may initiate anti-tumor immune responses that could provide lasting benefits in late-stage ovarian cancer."

"SL-172154 is emerging as a highly differentiated CD47 inhibitor. The clinical data indicate that this compound can safely engage CD40 in a manner that has evaded other CD40-targeted biologics for over twenty years. At the same time, we can compare and contrast the relative potency of CD40 versus OX40 activation, and the clinical data indicate that CD40 targeting provides substantially more immunologic activity than OX40 activation. There are some parallels to these observations in the checkpoint space, where blockade of targets like LAG3, TIM3, and TIGIT has been far more subtle than blockade of CTLA-4 or PD-1," continued Dr. Schreiber. "The current data suggests that we may be coming close to a recommended Phase 2 dose selection for SL-172154 as monotherapy. We are excited to transition to the combination with liposomal doxorubicin in ovarian cancer, and with azacitidine and venetoclax in AML, and azacitidine in higher-risk MDS and TP53 mutant AML. More importantly, these data help to establish the ARC platform more broadly as a novel class of biologic medicine, which opens opportunities for the rest of our vast pipeline of candidates developed internally at Shattuck."

Third Quarter 2021 Recent Business Highlights and Other Recent Developments

Agonist Redirected Checkpoint (ARC) Platform Clinical-Stage Pipeline

Initial Data from Ongoing SL-172154 (SIRPα-Fc-CD40L) Phase 1 Dose-Escalation Clinical Trial in Platinum Resistant Ovarian Cancer Demonstrate Favorable Safety Profile and High Target Occupancy at the 36th Annual SITC (Free SITC Whitepaper) Meeting: The Phase 1 trial is an open-label, multi-center, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with platinum resistant ovarian cancer. Shattuck will continue dose escalation to 10mg/kg.

Data reported at SITC (Free SITC Whitepaper) was in 14 evaluable patients as of July 6, 2021, across four dose levels on two schedules: schedule 1 (day 1, 8, 15, 29, then every two weeks) at 0.1, 0.3 mg/kg and schedule 2 (weekly) at 0.3, 1.0, 3.0 mg/kg. To date, no dose limiting toxicities have been observed.
Preliminary pharmacodynamic parameters for SL-172154 demonstrate on-target, CD40-mediated immune activation. The binding of SL-172154 to CD40+ B cells and monocytes led to rapid activation and margination of these cells post infusion.
High target occupancy was observed on CD47+ leukocytes at the doses studied, with preferential binding to leukocytes as compared to red blood cells.
Cyclical increases in certain innate and adaptive serum cytokines were consistent with CD40 receptor engagement and activation following dosing. There were no notable increases in IL-6 or TNFα, or evidence of bell-shaped dose responses.
SL-172154 has been well tolerated at doses which achieve near-complete target occupancy for both CD40 and CD47, with evidence of on-target pharmacodynamic activity which has not yet plateaued, warranting further dose escalation.
Combination Study of SL-172154 with Liposomal Doxorubicin Expected to Begin First Half of 2022: A Phase 1B clinical trial of SL-172154 in combination with liposomal doxorubicin to evaluate safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamics is planned to begin enrolling in the first half of 2022. Shattuck continues to evaluate additional combination agents for SL-172154 for the treatment of patients with ovarian cancer.
Open IND for SL-172154 in AML and HR-MDS: Shattuck submitted an investigational new drug application to the U.S. Food and Drug Administration for a Phase 1A/B clinical trial for SL-172154 in patients with acute myeloid leukemia, or AML and, higher-risk myelodysplastic syndromes, or HR-MDS, in September. The IND is now open, and the trial will evaluate safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, as both monotherapy and in combination. In AML, Shattuck plans to evaluate SL-172154 in combination with both azacitidine and venetoclax. In both HR-MDS and TP53 mutant AML, Shattuck plans to evaluate SL-172154 in combination with azacitidine. Initial data from the trial are expected in the second half of 2022.
Continued Enrollment of SL-172154 Phase 1 Clinical Trial in Squamous Cell Carcinoma of the Head and Neck or Skin: Shattuck continues to enroll patients in a Phase 1 clinical trial for SL-172154, in patients with squamous cell carcinoma of the head and neck or skin. The Phase 1 trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, administered intratumorally as monotherapy. Initial dose-escalation data from the trial are expected in the first half of 2022.
Initial Data from Ongoing SL-279252 (PD1-Fc-OX40L) Phase 1 Dose-Escalation Clinical Trial in Advanced Solid Tumors Demonstrate Evidence of Anti-Tumor Activity at the 36th Annual SITC (Free SITC Whitepaper) Meeting: The ongoing Phase 1 trial is an open-label, multi-center, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-279252 as monotherapy in patients with advanced solid tumors. Today, Shattuck reported continued enrollment at the next dose level, 12 mg/kg.

Data reported at SITC (Free SITC Whitepaper) as of June 11, 2021, was in 43 patients, dosed intravenously, with 30 patients treated on schedule 1 (day 1, 8, 15, 29, then every 2 weeks) from dose level 0.0001-6 mg/kg, and 13 patients treated on schedule 2 (weekly) from dose level 0.3-3 mg/kg. SL-279252 was well-tolerated in heavily pretreated subjects with refractory solid tumors with no maximum tolerated dose reached. A total of 16 patients were treated at doses of 1 mg/kg or higher on schedule 1.
Best response was one confirmed partial response (iPR) (ocular melanoma, four prior systemic regimens, including PD-1 and CTLA-4 inhibitors) in a patient who remained on treatment for more than one year, and stable disease (iSD) in 12 patients (including 1 unconfirmed iPR). iSD for > 24 weeks occurred in 5/12 patients.
58% of patients had received PD-1/L1 therapy, and of available tumor biopsies most tumors lacked PD-L1 expression as measured by TPS.
SL-279252 exhibited high OX40 target engagement and OX40-dependent PD effects.
Shattuck is currently enrolling patients with known PD-L1 positive tumors at dose levels of 12 mg/kg, to fully characterize PK, PD, and anti-tumor activity.
Corporate Updates

Shattuck and Takeda Mutually Agree to Termination of Collaboration Agreement: In November 2021, Shattuck and Takeda mutually agreed to termination of the Collaboration Agreement for SL-279252 and SL-115154, originally executed in 2017. Shattuck is no longer required to satisfy any remaining performance obligations, the Company will not make any payments to or receive any future milestone or royalty payments from Takeda, and all options to license and rights of first negotiation held by Takeda under the Collaboration Agreement were terminated.
Changes to Shattuck’s Board: In October 2021, Shattuck announced changes to its board of directors.

Dr. Carrie Brownstein was appointed to the board and serves as a member of the Nominating and Corporate Governance Committee. Dr. Brownstein brings over 15 years of clinical research and development experience having held clinical leadership roles at Roche, Regeneron, Celgene and Cellectis and as a practicing pediatric hematologist oncologist.
Dr. George Golumbeski was appointed chairman of the Board. Dr. Golumbeski has served on Shattuck’s Board as an independent director since 2018. Dr. Golumbeski replaces Josiah Hornblower as chairman of the board. Mr. Hornblower resigned from the board in October 2021.
Third Quarter 2021 Financial Results

Cash Position: As of September 30, 2021, cash and cash equivalents and short-term investments were $290.2 million, as compared to $335.4 million as of December 31, 2020.
Research and Development (R&D) Expenses: R&D expenses for the third quarter ended September 30, 2021, were $15.1 million, as compared to $11.8 million for the third quarter ended September 30, 2020. The increase was primarily driven by increases in clinical development, personnel-related costs, and laboratory capabilities.
General and Administrative (G&A) Expenses: G&A expenses for the third quarter ended September 30, 2021, were $4.3 million, as compared to $2.5 million for the third quarter ended September 30, 2020. The increase was primarily driven by an increase in personnel related costs to support the operational expansion and costs associated with being a public company.
Net Loss: Net loss was $17.4 million for the third quarter ended September 30, 2021, or $0.41 per basic and diluted share, as compared to a net loss of $11.8 million for the third quarter ended September 30, 2020, or $1.54 per basic and diluted share.
2021 Financial Guidance

Shattuck believes its cash and cash equivalents and short-term investments will be sufficient to fund its operations into the second half of 2024, which is beyond results from its Phase 1 clinical trials of SL-172154 and SL-279252. The reduction in cash runway guidance from our last issued guidance is primarily attributable to increased clinical activities for SL-172154 and ongoing process development and manufacturing to support our ongoing and future clinical trials, including the development of a manufacturing process suitable for registrational trials. This cash runway guidance is based on the Company’s current operational plans and excludes any additional funding that may be received or business development or additional clinical development activities that may be undertaken.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancers. Two Phase 1 clinical trials are ongoing, the first for patients with advanced and platinum resistant ovarian cancer (NCT04406623) and the second for patients with advanced squamous cell carcinoma of the head, neck or skin (NCT04502888).

About SL-279252

SL-279252 (PD1-Fc-OX40L) is an investigational ARC fusion protein designed to simultaneously inhibit the PD-1/PD-L1 checkpoint interaction and activate the OX40 costimulatory receptor to bolster an anti-tumor immune response receptor in patients with advanced solid tumors. A Phase 1 trial in patients with solid tumors and lymphoma is ongoing (NCT03894618).

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Category: Uncategorized

Fusion Pharmaceuticals Announces Third Quarter 2021 Financial Results and Clinical Program Update

Study Shows Biocept’s Switch-Blocker Technology Enhances Performance of Conventional PCR-Based Liquid Biopsy Assays in Detecting Rare Cancer Mutations

Ascendis Pharma A/S Presents New Non-Clinical Data for TransCon™ TLR7/8 Agonist Oncology Program at SITC 2021

Acorda Therapeutics Announces Agreement to Commercialize INBRIJA® in Germany

Shattuck Labs Reports Third Quarter 2021 Financial Results and Recent Business Highlights