March 2022 – Page 109 – 1stOncology™: Cancer Intelligence Service

Fusion Pharmaceuticals Announces Fourth Quarter 2021 Financial Results and Clinical Program Updates

On March 17, 2022 Fusion Pharmaceuticals Inc. (Nasdaq: FUSN), a clinical-stage oncology company focused on developing next-generation radiopharmaceuticals as precision medicines, reported financial results for the fourth quarter ended December 31, 2021 and provided an update on clinical and corporate developments (Press release, Fusion Pharmaceuticals, MAR 17, 2022, View Source [SID1234610258]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

Chief Executive Officer John Valliant, Ph.D. commented, "In 2021, we made progress leveraging our platform technology and research engine to build a diverse pipeline of targeted alpha therapies (TATs) from different classes of targeting molecules to pursue validated cancer targets in areas of high unmet medical need."

Dr. Valliant continued, "We continue to execute on our Phase 1 trial of FPI-1434 in patients with solid tumors, and look forward to reporting data from this trial in the second half of this year. Our subsequent programs are progressing, with the investigational new drug application (IND) for FPI-1966 cleared in 2021, and the submission of an IND for FPI-2059, our first small molecule program, expected in the first half of this year. In addition, under our collaboration, we have agreed with AstraZeneca to progress to IND-enabling studies a new bispecific antibody-based TAT. We also recently entered two strategic partnerships to discover novel, peptide-based radiopharmaceuticals, both demonstrating the versatility and potential applicability of the Fusion platform. In parallel, we have expanded our leadership team, deepening our radiopharmaceutical and oncology expertise, and progressed our manufacturing and actinium supply initiatives, supporting our pipeline growth and clinical plans. Amid a resurgence of excitement about the potential for radiopharmaceuticals becoming a pillar of cancer therapy, Fusion is well-positioned as a leader in the space."

Clinical Update

FPI-1434

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. The Company continues to anticipate reporting Phase 1 safety, pharmacokinetics, and imaging data, including any evidence of anti-tumor activity, and details on the dosing paradigm, in the second half of 2022. 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.

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 now expects to dose the first patient in the second quarter of 2022 rather than the first quarter and expects preliminary pharmacokinetic and imaging data from the first patient cohort in the second quarter of 2023. The shift is a result of delays in study site initiations related to the COVID-19 pandemic.

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 solid tumors. FPI-2059 combines Ipsen’s IPN-1087 (previously studied as a beta-emitting radiopharmaceutical), 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.

Silence Therapeutics Reports Fourth Quarter and Full Year 2021 Results

On March 17, 2022 Silence Therapeutics plc, Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported its financial results for the fourth quarter and full year ended December 31, 2021 and reviewed recent business highlights (Press release, FierceBiotech, MAR 17, 2022, View Source [SID1234610257]).

"2021 was a remarkable year for Silence," said Craig Tooman, President and Chief Executive Officer at Silence. "We successfully delivered the first clinical data from our proprietary mRNAi GOLD platform, advanced two wholly owned programs in the clinic and made excellent progress across both our proprietary and partnered pipelines. This momentum has continued into 2022 with the positive SLN360 data and we look forward to the late breaking presentation at ACC on April 3rd. With clinical data now demonstrated in two separate programs, we are optimistic about what we can deliver from our platform and look forward to a very exciting year ahead."

Rhonda Hellums, Chief Financial Officer at Silence commented, "We continued to benefit from our hybrid business model in 2021, receiving around $58 million in non-dilutive capital from our collaborations. We moved exclusively to the Nasdaq and significantly expanded our global shareholder base. We ended the year with £73.5 million in cash, cash equivalents and term deposits and we will continue to prioritize non-dilutive financing solutions."

Fourth Quarter 2021 Business Highlights

mRNAi GOLD Proprietary Program Updates

SLN360 Lp(a) Lowering Program

Extended follow-up period in the single-ascending dose cohorts up to 365 days to further assess the duration of action.
Established therapeutic dose range based on single-ascending dose cohorts 1-4 to proceed to the multiple-ascending dose portion.
SLN124 Hepcidin Regulation Program

Presented clinical data from the SLN124 healthy volunteer study at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Key data included:
All 3 dose levels were well tolerated with no serious or severe treatment emergent adverse events (TEAEs) or TEAEs leading to withdrawal.
Average hepcidin, a key endogenous regulator of iron balance and distribution, increased up to ~4-fold after a single dose with effect sustained for at least 2 months.
Serum iron reduced by ~50% after a single dose with effect sustained for at least 2 months.
mRNAi GOLD Partnered Program Updates

Secured new collaboration with Hansoh Pharma to develop therapeutics leveraging the Silence mRNAi GOLD platform, providing the Company with exclusive rights to two undisclosed targets in all territories except the China region (Greater China, Hong Kong, Macau and Taiwan). Hansoh received an exclusive option to license rights to those two targets in the China region and global rights to a third undisclosed target.
Post Year-end Highlights

Announced positive topline data in the SLN360 phase 1 single-ascending dose study in 32 healthy adults with high Lp(a) (≥ 60 mg/dL or 150 nmol/L). Topline data included:
SLN360 was well tolerated with no clinically important safety concerns identified.
SLN360 reduced Lp(a) in a dose dependent manner from 46% up to a maximum of 98% with up to an 81% reduction persisting at 150 days.
Detailed results from the SLN360 phase 1 single-ascending dose study will be presented in a late-breaker at the American College of Cardiology (ACC) Annual Meeting on April 3, 2022.
Started dosing in the SLN360 phase 1 multiple-ascending dose study in adults with high Lp(a) that have a confirmed history of stable atherosclerotic cardiovascular disease ("ASCVD").
Completed enrollment in the SLN124 phase 1 single-ascending dose study in thalassemia patients and remain on-track to report topline data in the third quarter of 2022.
SLN124 granted FDA orphan drug designation in polycythemia vera (PV) and the Company remains on-track to start a phase 1 study in PV in the second half of 2022.
Discontinued further enrollment in the myelodysplastic syndrome (MDS) arm of the SLN124 phase 1 program due to recruitment challenges in this population and the decision to prioritize spend in thalassemia and PV indications where the Company believes it can derive the most value in the near term.
2021 Financial Results

For the twelve-month period ending December 31, 2021, the net loss after tax was £39.4 million, or weighted average loss per share 44.3 pence compared to the same period in 2020 of £32.5 million, or weighted average loss per share 39.8 pence. The increase in net loss was primarily related to increase in R&D expenditures as the Company continues to further advance and expand its pipeline of novel medicines.

Revenue

Revenue recognized for the year ending December 31, 2021 was £12.4 million, compared to £5.5 million for the year ending December 31, 2020. The Company records revenue from collaborations based on percentage of contract completion and the increase was driven by the advancement of current collaboration programs, as well as the execution of new collaboration agreements in 2021. Therefore, as the Company’s current collaboration programs progress and additional programs are initiated revenues are also expected to increase over time.

Cost of sales

The cost of sales increased for the twelve months ending December 31, 2021 to £7.5 million from £3.8 million in the period ending December 31, 2020. Cost of sales includes research and development expenditure that is directly related to work carried out on revenue generating contracts. The increase was largely due to the further advancement and initiation of new collaboration programs.

Research and Development

During the year ending December 31, 2021, research and development expenditures increased by £10.6 million to £30.8 million from £20.2 million in the year ending December 31, 2020. The increase is a result of additional clinical studies and an increase in contract manufacturing activities for Silence’s proprietary programs, as well as an increase in personnel costs to expand the internal capabilities and expertise to further advance the Company’s siRNA platform.

General and Administrative

General and administrative expenses increased by £6.0 million to £20.0 million for the year ending December 31, 2021 from £14.0 million for the same corresponding period in 2020. This increase was predominantly related to requirements for public company compliance and support of the R&D portfolio including personnel.

Liquidity, cash and cash equivalents

As of December 31, 2021, the Company had £73.5 million of cash and cash equivalents. During 2021, the Company received $40.0 million or £30.8 million from its partner AstraZeneca, and milestones totaling $4.0 million or £2.9 million from its partner Mallinckrodt. The Company also received a $16.0 million upfront payment, or £10.7 million net of taxes, from the execution of a collaboration agreement with Hansoh in the fourth quarter of 2021. Since 2019, Silence has received over $100 million in upfront and milestone payments from its collaboration partners. These proceeds provide non-dilutive capital for the continued development and advancement of the Company’s proprietary and partnered product candidates. The Company believes that its cash and cash equivalents of £73.5 million as of the end of December 2021 is sufficient to fund its operations through early 2023.

MSD’s KEYTRUDA® (pembrolizumab) Significantly Improved Disease-Free Survival (DFS) Versus Placebo as Adjuvant Therapy in Patients With Stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC) Regardless of PD-L1 Expression

On March 17, 2022 MSD, a trade name of Merck & Co., Inc, Kenilworth, NJ, USA., the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP) reported results from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS (Press release, EORTC, MAR 17, 2022, View Source [SID1234610256]). The study found that adjuvant treatment with KEYTRUDA significantly improved disease-free survival (DFS), one of the dual primary endpoints, reducing the risk of disease recurrence or death by 24% compared to placebo (hazard ratio [HR]=0.76 [95% CI, 0.63-0.91]; p=0.0014) in patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression. Median DFS was 53.6 months for KEYTRUDA versus 42.0 months for placebo, an improvement of nearly one year. These data are being presented today during a European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Plenary and will be shared with regulatory authorities worldwide.

"These are the first positive results for KEYTRUDA in the adjuvant setting for non-small cell lung cancer, and represent the sixth positive pivotal study evaluating a KEYTRUDA-based regimen in earlier stages of cancer," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, MSD. "KEYTRUDA has become foundational in the treatment of metastatic non-small cell lung cancer, and we are pleased to present these data showing the potential of KEYTRUDA to help more patients with lung cancer in earlier stages of disease. We thank the patients, their caregivers and investigators for participating in this study."

As previously announced, there was also an improvement in DFS for patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%) treated with KEYTRUDA compared to placebo, the other dual primary endpoint; these results did not reach statistical significance per the pre-specified statistical plan (HR=0.82 [95% CI, 0.57-1.18]; p=0.14). Among these patients, median DFS was not reached in either arm. Additionally, a favorable trend in overall survival (OS), a key secondary endpoint, was observed for KEYTRUDA versus placebo regardless of PD-L1 expression (HR=0.87 [95% CI, 0.67-1.15]; p=0.17); these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial will continue to evaluate DFS in patients whose tumors express high levels of PD-L1 (TPS ≥50%) and OS. The safety profile of KEYTRUDA in this study was consistent with that observed in previously reported studies.

"Lung cancer is most treatable at earlier stages, and adding treatment after surgery may help reduce the risk of recurrence," said Professor Mary O’Brien, consultant medical oncologist and head of the Lung Unit at The Royal Marsden NHS Foundation Trust and professor of practice (medical oncology) at Imperial College London, as well as co-principal investigator. "We are encouraged by these new Phase 3 data, as they represent the first time adjuvant immunotherapy has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with stage IB-IIIA non-small cell lung cancer."

"While significant advancements have been made in the treatment of metastatic non-small cell lung cancer, there remains an unmet need for patients with earlier stages of this disease, as up to 43% of them will experience disease recurrence following surgery," said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain and co-principal investigator. "The positive disease-free survival data observed in this study with the use of KEYTRUDA in the adjuvant setting has the potential to have important implications for how we treat patients with stage IB-IIIA non-small cell lung cancer."

In addition to KEYNOTE-091, five other pivotal trials evaluating a KEYTRUDA-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials included: KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer.

MSD has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012.

Study Design and Additional Data From KEYNOTE-091

KEYNOTE-091, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, is a randomized, Phase 3 trial (ClinicalTrials.gov, NCT02504372) sponsored by MSD and conducted in collaboration with EORTC and ETOP evaluating KEYTRUDA compared to placebo for the adjuvant treatment of patients with stage IB (≥4 centimeters) to IIIA NSCLC following surgical resection (lobectomy or pneumonectomy) and with adjuvant chemotherapy when indicated. The dual primary endpoints are DFS in the overall population and in patients whose tumors express PD-L1 (TPS ≥50%). Disease-free survival is calculated as the time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy, or death from any cause, whichever occurs first. The secondary endpoints include OS and lung cancer-specific survival (the time from randomization to date of death due to lung cancer specifically). The study randomized 1,177 patients (1:1) to receive either KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for one year or maximum 18 doses; n=590); or placebo (IV Q3W for one year or maximum 18 doses; n=587). The median number of doses was 17 for KEYTRUDA and 18 for placebo. As of data cut-off for this interim analysis (September 20, 2021), median time from randomization to data cut-off was 35.6 months (range, 16.5-68.0 months).

Grade ≥3 adverse events occurred in 34.1% of patients receiving KEYTRUDA and 25.8% of patients receiving placebo. Adverse events resulting in discontinuation of any treatment occurred in 19.8% of patients receiving KEYTRUDA and 5.9% of patients receiving placebo; there were four treatment-related deaths in the KEYTRUDA arm and no treatment-related deaths in the placebo arm.

CytomX Therapeutics to Present Updated Preclinical Data for Conditionally Activated Cytokine Program at AACR Annual Meeting 2022

On March 17, 2022 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated oncology therapeutics, reported that preclinical data supporting the ongoing development of its conditionally activated cytokine program will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 8-13, 2022, at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, CytomX Therapeutics, MAR 17, 2022, View Source [SID1234610255]).

"Type I interferons, as monotherapy or in combination with PD-(L)1 blockade, are powerful antitumor agents, but the toxicity of these therapies, including interferon alpha, can limit their clinical use. We are working to address this limitation with our conditionally activated cytokine program," said Marcia P. Belvin, Ph.D., senior vice president and head of research at CytomX Therapeutics. "At the upcoming AACR (Free AACR Whitepaper) Annual Meeting, we will report encouraging preclinical data that support the development of our conditionally activated interferon alpha-2b therapeutic candidate as a promising addition to current immunotherapy regimens, potentially expanding benefit to patients with typically unresponsive tumors. This program represents the leading edge of a broad initiative at CytomX towards enhancing the therapeutic window of multiple cytokines."

Details for the poster presentation are as follows:
Presentation Title: Probody-interferon-alpha 2b combines antitumor activity with improved tolerability
Abstract Number: 2071
Session Title: Immunomodulatory Agents and Interventions 1
Session Date and Time: Monday, April 11, 2022, 1:30 – 5:00 pm CT

CORMEDIX INC. ANNOUNCES THE APPOINTMENT OF CHIEF EXECUTIVE OFFICER

On March 17, 2022 CorMedix Inc. (Nasdaq: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of infectious and inflammatory disease, reported the appointment of Joseph Todisco as Chief Executive Officer of the company (Press release, CorMedix, MAR 17, 2022, View Source [SID1234610254]). Mr. Todisco also will join the CorMedix Board of Directors. The company expects Mr. Todisco to join CorMedix on May 16th or such earlier date as he completes his contractual responsibilities to his current employer.

Myron Kaplan, Chairman of CorMedix’s Board of Directors commented, "We are delighted to welcome Joe to CorMedix as the new Chief Executive Officer. Having built pharmaceutical businesses in the past and led successful commercial organizations globally, Joe brings significant and relevant experience to the company. The Board believes he is the right person to lead CorMedix as we continue to advance DefenCath and aim to build a successful commercial franchise around our lead product. The Board also is grateful for Dr. Matt David’s leadership throughout the interim period and we look forward to continuing to work with him and the executive team."

"CorMedix has a strong late-stage pre-commercial asset in DefenCath with a compelling value proposition for patients in the hemodialysis community," said Mr. Todisco. "I am excited to be taking on this role, and I look forward to working alongside the CorMedix board, management, and employees to continue building the company as we prepare for a potential commercial launch in hemodialysis and explore new opportunities for growth."

"With the recent announcement of our resubmission of the DefenCath NDA to the FDA, the CorMedix team has been active on all fronts as we have worked through manufacturing challenges and continued to build our understanding of the commercial opportunity for DefenCath," said Dr. Matt David, interim CEO and Chief Financial Officer. "I join my colleagues in welcoming Joe to CorMedix as Chief Executive Officer. I look forward to working closely with Joe as we seek to transform CorMedix to a commercial stage entity."

Joe Todisco is an experienced pharmaceutical industry leader with a track record of building businesses globally and providing commercial leadership over the last 20 years. Previously, Mr. Todisco was a senior executive at Amneal Pharmaceuticals, where for the past 11 years he has held various roles, most recently as Executive Vice President, Chief Commercial Officer where he was responsible for Amneal Specialty, a growing branded products business with $380 million in revenue and approximately 200 employees. During his tenure at Amneal, Mr. Todisco held roles overseeing corporate development and international operations, leading commercial teams in several international markets including the UK, Australia and Germany, as well as leading Amneal’s merger integration with Impax Laboratories in 2018.

Mr. Todisco was previously Co-Founder and managing executive of Gemini Laboratories, a specialty pharmaceutical company focused on the sales and marketing for niche branded products in the US Market. Gemini Laboratories was established as an affiliate of Amneal Pharmaceuticals and was subsequently acquired by Amneal in 2018.

Prior to joining Amneal, Mr. Todisco was Vice President, Business Development & Licensing at Ranbaxy, Inc. where he was responsible for developing and executing Ranbaxy’s North American commercial business strategy. Prior to Ranbaxy, he held various roles at Par Pharmaceutical, and in his earlier career held positions at Oppenheimer & Company and Marsh & McLennan Companies. Mr. Todisco obtained his MBA in finance from Fordham Graduate School of Business and his BA in Economics from Georgetown University.

1stOncology is recognized as a
Top 10 Global Pharma Analytic Provider

Continue your journey with 1stOncology by accessing our Free Leading Cancer Conference Whitepapers, signing up for our Free Weekly Newsletter and requesting a Free Demo to see how we can help you be 1st in Oncology!

Month: March 2022

Fusion Pharmaceuticals Announces Fourth Quarter 2021 Financial Results and Clinical Program Updates

Silence Therapeutics Reports Fourth Quarter and Full Year 2021 Results

MSD’s KEYTRUDA® (pembrolizumab) Significantly Improved Disease-Free Survival (DFS) Versus Placebo as Adjuvant Therapy in Patients With Stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC) Regardless of PD-L1 Expression

CytomX Therapeutics to Present Updated Preclinical Data for Conditionally Activated Cytokine Program at AACR Annual Meeting 2022

CORMEDIX INC. ANNOUNCES THE APPOINTMENT OF CHIEF EXECUTIVE OFFICER