On November 15, 2021 UroGen Pharma Ltd. (Nasdaq: URGN), a biopharmaceutical company dedicated to building and commercializing novel solutions that treat urothelial and specialty cancers, reported financial results for the third quarter ended September 30, 2021, and provided an overview of the Company’s recent developments (Press release, UroGen Pharma, NOV 15, 2021, View Source [SID1234595582]).

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"The third quarter of 2021 was one of continued progress at UroGen, both clinically and commercially," said Liz Barrett, President and Chief Executive Officer of UroGen. "As we highlighted at our Spotlight Event last week, we will initiate a new single-arm Phase 3 study of UGN-102 in low-grade, intermediate-risk, non-muscle invasive bladder cancer. We believe this new design affords a higher probability of regulatory success for UGN-102 in patients with low-grade IR-NMIBC, while allowing us to remain on-track for a planned NDA submission in 2024." She added, "Additionally, as we approach the close of 2021, we are pleased with the strong demand we’re seeing for Jelmyto. September and October marked our highest months ever for both new patient starts and patient enrollment forms. We look forward to a strong start to 2022, as we advance and grow our pipeline while furthering the adoption of Jelmyto with the goal of it becoming the standard of care for patients with low-grade UTUC."

Business Highlights:

Jelmyto (mitomycin) for pyelocalyceal solution:

Achieved highest-ever Patient Enrollment Forms and New Patient Starts in September and October 2021.
UroGen generated net product revenue of $11.4 million for the third quarter of 2021, representing over 200% growth over the third quarter of 2020 (first full quarter of launch), this compares to $13.0 million in the second quarter of 2021.
As of November 1, 2021, 706 sites have been activated, which means they have completed their internal processes and have treated or are ready to treat patients. This represents a 73% increase since August 1, 2021.
Sites that have treated more than one patient as of November 1, 2021, increased to 86, compared to 63 as of August 1, 2021: an increase of approximately 37%.
UGN-102 (mitomycin) for intravesical solution:

Following discussions with the U.S. Food & Drug Administration (FDA), the Company announced plans to conduct a new single-arm Phase 3 study of UGN-102 for the treatment of low-grade, intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The trial, which is expected to initiate in early 2022, will be similar in design to the Company’s previous OPTIMA II study. Based on the results of the OPTIMA II study, the Company believes this new trial carries a high probability of demonstrating a significant benefit for patients.
Based on the planned initiation of this new Phase 3 study of UGN-102, the Company has ceased enrollment in the ATLAS Phase 3 trial of UGN-102 in LG-IR-NMIBC. The Company plans to complete ongoing treatments and follow up for all patients currently enrolled in the therapy arm. Safety data from the ATLAS study is expected to be included in a planned regulatory submission for UGN-102.
UGN-301:

Preclinical studies conducted to-date suggest that bladder cancer treated with a combination of TLR-7 agonist and an anti-CTLA4 antibody in RTGel, produces improved survival compared to treatment with other checkpoint inhibitors in RTGel, either alone or in combination with UGN-201.
Non-human primate toxicity studies underway to facilitate the initiation of a multi-arm Phase 1 study of UGN-301 in combination with other agents.
First-in-human study planned to start in the first half of 2022.
Geographic expansion:

Initiated a named-patient access program for Jelmyto in France, Germany, Switzerland, Austria and the UK.
Third Quarter 2021 Financial Results:

Jelmyto Revenue: UroGen reported net product revenue of Jelmyto for the third quarter ended September 30, 2021 of $11.4 million. Net product revenue was $31.9 million for the first three quarters of 2021 compared to $3.8 million for the same period in 2020 due to the launch of Jelmyto in June 2020.

R&D Expense: Research and development expenses for the third quarter ended September 30, 2021 were $11.9 million, including non-cash share-based compensation expense of $1.0 million. This compares to $10.2 million, including non-cash share-based compensation expense of $1.5 million, for the same period in 2020. The increase of $1.7 million is primarily attributable to the launch of our Phase 3 ATLAS study for UGN-102 at the end of 2020, and development cost of UGN-301, partially offset by a decrease in R&D expense related to Jelmyto.

SG&A Expense: Selling, general and administrative expenses for the third quarter ended September 30, 2021 were $21.6 million, including non-cash share-based compensation expense of $4.5 million. This compares to $22.1 million, including non-cash share-based compensation expense of $5.2 million, for the same period in 2020. The $0.5 million decrease is primarily attributable to higher launch related commercial spend in 2020.

Financing on Prepaid Forward Obligation: UroGen reported financing expense related to the prepaid forward obligation to RTW Investments of $6.8 million for the third quarter ended September 30, 2021.

Net Loss: UroGen reported a net loss of $30.2 million, or basic and diluted net loss per ordinary share of $1.35, for the third quarter ended September 30, 2021. This compares to $28.8 million, or basic and diluted net loss per ordinary share of $1.31, for the same period in 2020.

Cash & Cash Equivalents: As of September 30, 2021, cash, cash equivalents and marketable securities totaled $110.3 million.

2021 Operating Expense and Revenue Guidance: The Company is reducing its anticipated full year 2021 operating expenses to the range of $137 million to $142 million, from $155 million to $165 million, the new guidance includes non-cash share-based compensation expense of $22 to $25 million, subject to market conditions. In addition, the Company is providing full year 2021 revenue guidance of $47 million to $51 million.

Conference Call & Webcast Information:

Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review the Company’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. Alternatively, please call (855) 765-5685 (U.S.) or (615) 247-5916 (International) to listen to the live conference call. The conference ID number for the live call will be 1908609. An archive of the webcast will be available for two weeks on the Company’s website.

About Jelmyto

Jelmyto (mitomycin) for pyelocalyceal solution, is a drug formulation of mitomycin indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Utilizing the RTGel technology platform, UroGen’s proprietary sustained release, hydrogel-based formulation, Jelmyto is designed to enable longer exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. Jelmyto is delivered to patients using standard ureteral catheters or nephrostomy tube. The U.S. FDA previously granted Orphan Drug, Fast Track, and Breakthrough Therapy Designations to Jelmyto for the treatment of LG-UTUC. On April 15, 2020, the FDA approved Jelmyto, making it the first drug approved for the treatment of LG-UTUC in adult patients.

APPROVED USE FOR JELMYTO

JELMYTO is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC).

IMPORTANT SAFETY INFORMATION

You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract.

Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you:

are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO.
Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose.

Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose.

are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose.
Tell your healthcare provider if you take water pills (diuretic).
How will I receive JELMYTO?

Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment.
You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses.
JELMYTO is given to your kidney through a tube called a catheter.
During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines.
After receiving JELMYTO:

JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours.
To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water.
Clothing that comes in contact with urine should be washed right away and washed separately from other clothing.
JELMYTO may cause serious side effects, including:

Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO.
Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO.
The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda/gov/medwatch or call 1‑800‑FDA‑1088. You may also report side effects to UroGen Pharma at 1-855-987-6436.

Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information.

About Upper Tract Urothelial Cancer (UTUC)

Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 – 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an investigational drug formulation of mitomycin in Phase 3 development for the treatment of low-grade intermediate risk non-muscle invasive bladder cancer. Utilizing the RTGelTM Technology Platform, UroGen’s proprietary sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter. The Company presented results from the Phase 2b OPTIMA II trial in September 2021.

About the Phase 3 ATLAS Trial

ATLAS was a global, open-label, randomized controlled Phase 3 trial designed to assess the efficacy and safety of UGN-102, with or without transurethral resection of bladder tumor (TURBT), versus TURBT alone in patients diagnosed with low-grade intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC), defined as 1 or 2 of the following: new or recurrent multifocal bladder tumors, a solitary new or recurrent tumor >3 cm, or LG-IR-NMIBC recurrence in less than 12 months following a prior tumor diagnosis requiring endoscopic surgical resection or ablation.

Patients were randomized 1:1 to either UGN-102 or TURBT. Patients in the UGN-102 arm were treated with six weekly intravesical instillations of UGN-102. At the 3-month time point, patients were assessed for response. Patients who have demonstrated a complete response to either UGN-102 or TURBT, will continue for long-term follow-up for evidence of recurrence. Patients who demonstrate presence of persistent disease at 3-months, in either arm, will undergo a TURBT and then will also continue for long-term follow up for evidence of recurrence. The primary endpoint of the study was disease free survival. On November 10, 2021, the Company announced that, following discussions with the U.S. Food & Drug Administration, it has ceased enrollment in the ATLAS study and plans to initiate a new, single-arm Phase 3 study of UGN-102 in early 2022. All patients enrolled in the treatment arm of ATLAS will continue to receive treatment and undergo follow up.

Learn more about the ATLAS trial at www.clinicaltrials.gov (NCT04688931)

On November 15, 2021 Ascendis Pharma A/S (Nasdaq: ASND) provided an update on the Company’s previously reported $25 million American Depositary Shares (ADS) Share Repurchase Program. Each ADS represents one ordinary share of Ascendis Pharma A/S (Press release, Ascendis Pharma, NOV 15, 2021, View Source [SID1234595581]). The program was executed under Rules 10b-18 and 10b5-1 of the U.S. securities regulations.

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Under the program initiated on November 1, 2021, Ascendis Pharma A/S has repurchased shares for an amount up to $25 million in the period from November 1, 2021 to November 9, 2021 and the program is completed.

Since the announcement as of November 8th, 2021, the following transactions have been executed.

Trade Date

Number of ADS
Weighted Average
Purchase Price

Total Value*
Accumulated, last announcement 122,422 $19,763,252
November 8, 2021 26,800 $161.84 $4,338,140
November 9, 2021 5,615 $159.99 $898,492
Purchased under the program 154,837 $161.43 $24,999,884
*Total value includes fees and costs associated with the repurchase program.

Following these transactions, Ascendis Pharma A/S repurchased a total of 154,837 ADSs under the Share Repurchase Program.

On November 15, 2021 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data from the Phase 2 expansion cohort of its ongoing Phase 1/2 clinical trial evaluating ONCT-216 (formerly TK216), an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins, in patients with relapsed or refractory Ewing sarcoma (Press release, Oncternal Therapeutics, NOV 15, 2021, View Source [SID1234595580]). The data update was delivered in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2021 Virtual Annual Meeting.

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Session Title: Session 12: Ultra-Rare and Translocation Sarcomas
Session Date: Saturday, November 13, 2021
Presentation Title: Paper 74 – TK216 FOR EWING SARCOMA- INTERIM PHASE 1/2 RESULTS
A copy of the presentation will be accessible on the Events & Presentations page of the Investors section on the Company’s website at investor.oncternal.com.

"We remain encouraged by the two complete responses to ONCT-216 in heavily pre-treated patients with relapsed or refractory Ewing sarcoma, including one patient who had a durable CR for 24 months on treatment, and remains with no evidence of disease off of all treatments for several months," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We believe that an intensified dosing schedule, which we are investigating in a new study cohort that is now enrolling, holds promise to address the significant unmet needs for patients suffering from this devastating disease."

ONCT-216 remains generally well tolerated. As of the October 1, 2021 data cutoff date, the most common drug-related adverse events included myelosuppression, fatigue, alopecia, nausea, pyrexia, and decreased appetite. The myelosuppression was primarily neutropenia, which was transient and readily managed. No unexpected off-target toxicities have been observed.

About Ewing sarcoma

Ewing sarcoma is the second most common bone tumor among children and adolescents. The median age at diagnosis of patients with Ewing sarcoma is 15, the incidence is about 3 cases per 1 million per year in children under the age of 20 and about 1.3 cases per 1 million overall in the U.S. and prevalence is about 12 per million people overall in the US. Nearly all Ewing sarcoma cases are driven by translocations of ETS family oncogenes, including 85-90% of cases driven by the EWS-FLI1 fusion, and approximately 10% by EWS-ERG. Patients diagnosed with metastatic disease have five-year survival rates between 18% and 30%. The prognosis for patients with recurrent Ewing sarcoma is particularly poor, and five-year survival after recurrence is approximately 10 to 15%.

About ONCT-216

ONCT-216 is an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as diffuse large B-cell lymphoma (DLBCL), prostate cancer and acute myeloid leukemia (AML). ONCT-216 was developed based on discoveries in the laboratory of Jeffrey Toretsky, M.D., at Georgetown Lombardi Comprehensive Cancer Center, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. ONCT-216 is an investigational medication that has not been approved by the FDA for any indication.

About the Study

ONCT-216 is being evaluated in a Phase 1/2 clinical study as a single agent and in combination with vincristine in heavily pretreated patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer with no standard treatment available after first-line chemotherapy. The current Phase 2 expansion cohort targeting up to 21 evaluable Ewing sarcoma patients is active and enrolling patients, designed to evaluate clinical responses to single agent ONCT-216 using an optimized dosing regimen, treating for 28 days per cycle, to intensify the amount of ONCT-216 administered over time. This multi-center study is currently enrolling patients at nine clinical trial centers across the U.S. Additional information about the ONCT-216 study may be accessed at ClinicalTrials.gov (NCT02657005).

On November 15, 2021 Recludix Pharma, a leader in platform approaches to discover inhibitors of challenging cancer and inflammatory disease targets, reported its launch with a proprietary platform technology, three SH2 domain inhibitor programs, and a new chief executive officer, Nancy Whiting, Pharm.D. Series A investors include NEA, Westlake Village BioPartners, and Access Biotechnology (Press release, Recludix Pharma, NOV 15, 2021, View Source [SID1234595578]).

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Recludix has built a proprietary platform to discover potent and selective inhibitors of challenging protein targets. The platform comprises custom generated DNA-encoded libraries, massively parallel determination of structure activity relationships, and a proprietary screening tool to ensure compound selectivity.

"Recludix has created highly differentiated technology and capabilities to harness the potential of targeting SH2 domains with potent and selective therapies," said Carol Gallagher, Pharm.D., venture partner at NEA. "We were especially attracted by the founders and the new terrain the company is exploring to create a pipeline of oral medicines that address previously undruggable, high-potential targets to treat patients with cancer and inflammatory diseases."

By integrating new chemical approaches and technologies, including custom DNA-encoded libraries and assays, Recludix is developing precision small molecule medicines against critical targets of interest, with the initial focus of its three lead programs of STAT3, STAT6, and an undisclosed non-STAT target. Abnormal STAT activation is found in numerous cancer types, including multiple leukemias, lymphomas and solid tumors, as well as inflammatory diseases, such as rheumatoid arthritis, asthma, atopic dermatitis, inflammatory bowel disease and others.

"The important role of the STAT family in disease signaling is well-characterized, but these proteins have remained elusive as targets for drug discovery until now. We believe Recludix’s platform will be a key differentiating factor leading to the successful development of treatments for these important targets," said Nancy Whiting, Pharm.D., chief executive officer of Recludix. "Our lead programs are targeting STAT3 and STAT6 through the novel mechanism of inhibition of their SH2 domains. With our proprietary technology, we believe we will be uniquely able to selectively and potently inhibit these important targets, resulting in more effective and better tolerated agents compared to the existing, less selective JAK/STAT targeting approaches."

Dr. Whiting is the newly appointed chief executive officer of Recludix and has an established track record in all phases of drug development. She is a 15-year veteran of Seagen, formerly Seattle Genetics. Most recently, Dr. Whiting was the executive vice president of corporate strategy. She previously served as executive vice president of late-stage development, senior vice president of clinical development and medical affairs, and head of experimental medicine. During her tenure at Seagen, Dr. Whiting played a central role in the development of ADCETRIS for lymphoma, PADCEV for bladder cancer, TUKYSA for breast cancer, TIVDAK for cervical cancer, and several other pipeline compounds. She completed her undergraduate training at the University of British Columbia and received her Pharm.D. from the University of Washington. Dr. Whiting serves on the Board of Directors of Caribou Biosciences.

Nicholas Lydon, Ph.D., FRS, is Recludix’s co-founder and chairman of the board of directors. Dr. Lydon is also a scientific founder of Blueprint Medicines and has served as a member of their board of directors since April 2011. Dr. Lydon has also served as a scientific advisor and member of the board of AnaptysBio (which he co-founded) and Ambit Biosciences. Dr. Lydon has extensive leadership experience in the discovery and development of small molecule therapies and protein kinase inhibitors, including as the vice president of small molecule drug discovery at Amgen, a founder of Kinetix Pharmaceuticals (acquired by Amgen), and at Ciba-Geigy AG (now Novartis AG). Dr. Lydon played a pivotal role in the discovery and development of GLEEVEC and was awarded the Lasker-DeBakey Clinical Medical Research Award, the Kettering Price from the General Motors Cancer Research Foundation and the Japan Prize for his role in its development. Dr. Lydon received a B.S. in biochemistry and zoology from the University of Leeds, England, and received a Ph.D. in biochemistry from the Medical Sciences Institute, University of Dundee, Scotland.

Additional members of Recludix’s senior leadership team include:

Patrick Zarrinkar, Ph.D., co-founder of Recludix, president and chief scientific officer, who has over 20 years of experience in drug discovery and technology development. His experience includes co-leading the development of the KINOMEscan kinase profiling platform, as well as part of Pfizer’s drug discovery and as part of the founding scientific team at Blueprint Medicines.
Daniel Treiber, Ph.D., co-founder of Recludix and vice president of discovery technology, has invented and developed multiple disruptive and commercially successful platforms addressing unmet needs in the areas of protein family-wide screening and profiling (KINOMEscan, BROMOscan, BCL2scan, E3scan), cellular target engagement (InCELL Pulse), and safety pharmacology (SAFETYscan47).
Brian Hodous, Ph.D., co-founder of Recludix and vice president of chemistry, has nearly 20 years of experience in drug discovery and preclinical development, including at Blueprint Medicines. Over his career, he contributed to the discovery of multiple clinical molecules and one approved drug, including: AYVAKIT (avapritinib) for PDGFRa mutant GIST and advanced systemic mastocytosis; fisogatinib for hepatocellular carcinoma; IPN60130 for fibrodysplasia ossificans progressiva, evobrutinib for multiple sclerosis, and AMG-900 for cancer.
Thomas W. Davis, Ph.D., vice president of biology, has over 20 years of experience in small molecule drug development, primarily in oncology and inflammation. He has worked on the COX2-selective inhibitor celecoxib, kinase inhibitor sunitinib, PTC299 (for various liquid cancers), PTC596 (for pediatric brain cancer), and the mutant p53 reactivator PMV586 (for patients harboring the Y220C p53 mutation).
Catherine Bovenizer, CPA, is the vice president of finance and business operations. She was previously the CFO of Renova Therapeutics and held finance leadership roles at Apricus Biosciences and Ambit Bioscience through its initial public offering and sale to Daiichi Sankyo.

On November 15, 2021 Redx Pharma (AIM: REDX), the clinical-stage biotechnology company focused on discovering and developing novel, small molecule, highly targeted therapeutics for the treatment of cancer and fibrotic disease, reported that the first patient has been dosed in the monotherapy arm of the Phase 2 clinical trial of its investigational drug RXC004 in patients with advanced microsatellite stable (MSS) metastatic colorectal cancer (mCRC) who have progressed following treatment with standard of care (Press release, Redx Pharma, NOV 15, 2021, View Source [SID1234595549]). RXC004 is Redx’s wholly-owned, highly potent and selective, orally active once-daily Porcupine inhibitor being developed as a targeted therapy for Wnt-ligand driven cancer.

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The multi-centre Phase 2 clinical trial (clinicaltrials.gov NCT04907539) will evaluate preliminary efficacy and safety of RXC004 in genetically-selected patients with Ring finger protein 43 (RNF43) or R-spondin (RSPO) aberrated, advanced MSS mCRC. Topline data is expected to report in the first half of 2023.

A second arm of the trial, evaluating RXC004 in combination with the anti-PD-1 antibody nivolumab in patients with MSS mCRC, is expected to commence in the first half of 2022 once a recommended dose has been established in the ongoing Phase 1 dose escalation combination trial.

D r Natalie Cook, University of Manchester and Christie NHS Foundation Trust, UK, and International Coordinating Investigator of the study in the UK, commented: "Microsatellite stable metastatic colorectal cancer is a devastating disease, with limited treatment options. A subgroup of these colorectal cancers possess RNF43 mutations or RSPO fusions leading to activation of the Wnt pathway as a driver of the cancer. This study will assess whether RXC004, a novel Porcupine inhibitor, has a clinically meaningful anti-cancer effect in this well-defined patient cohort.”

Lisa Anson, Chief Executive Officer of Redx Pharma, added: "We are excited to be dosing patients in Redx’s first ever Phase 2 clinical trial of a wholly-owned drug candidate, an important corporate milestone. Our encouraging Phase 1 results, recently reported at the ESMO (Free ESMO Whitepaper) Congress, combined with our preclinical data, strongly support the hypothesis that patients with Wnt-ligand driven tumours could benefit from RXC004."

A second Phase 2 clinical trial evaluating RXC004 as a monotherapy in advanced genetically selected pancreatic cancer and unselected biliary cancer is also expected to start in 2021.

About microsatellite stable metastatic colorectal cancer (MSS mCRC)
Metastatic colorectal cancers have a poor prognosis with a 5-year survival rate of approximately 15% (1). Standard first line and second line treatments are combinations of chemotherapy and a VEGF inhibitor or EGFR inhibitor. MSS cancers account for 95% of metastatic CRC and tend to be unresponsive to treatment with immune checkpoint inhibitors. In the third line treatment setting the response rate to standard agents is <5%, median progression free survival is approximately 2 months and overall survival approximately 6 months (2,3). Approximately 8% of MSS mCRC patients have Wnt-ligand driven tumours (3% RNF43 mutations and 5% RSPO fusions) (4)

About RXC004
RXC004 is a wholly owned, potent, selective, oral, small-molecule inhibitor of the Porcupine enzyme, a key activator of Wnt ligands in the Wnt-signalling pathway. The Wnt pathway is well established as a driver of both tumour growth and immune evasion. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which has also been linked to resistance to immune-checkpoint inhibitors (ICIs) such as nivolumab. By selecting patients with tumours that have high Wnt-ligand dependency, such as those with loss of function mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to allow the patient’s immune system to better recognise and attack the tumour.

ICIs such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt-pathway activation can enhance the ability of the tumour to evade destruction by the immune system and has been linked to lack of response to ICIs in these tumours. Redx scientists have observed in preclinical studies that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential to address some of the shortcomings of ICI therapies through increasing both response rates and duration of response, particularly in patient populations unresponsive to ICI therapy.