1stOncology™: Cancer Intelligence Service – Page 11542 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Aileron Therapeutics Initiates Enrollment in Schedule Optimization Part of Phase 1b/2 Study of ALRN-6924 as a Chemoprotection Agent in Small Cell Lung Cancer (SCLC) Patients Being Treated with Topotecan

On June 29, 2020 Aileron Therapeutics (NASDAQ:ALRN), a biotechnology company advancing a novel chemoprotective therapy for cancer patients, reported that it has enrolled the first patient in the open-label Phase 1b schedule optimization part of its ongoing Phase 1b/2 clinical trial, evaluating ALRN-6924’s potential to protect patients against chemotherapy-induced toxicities (Press release, Aileron Therapeutics, JUN 29, 2020, View Source [SID1234565066]). Patients in this open-label trial have p53-mutated extensive disease small cell lung cancer (SCLC) and are being treated with second-line topotecan following administration of ALRN-6924. The schedule optimization part of the trial is intended to determine whether ALRN-6924 given six hours before topotecan further enhances the protective effect of ALRN-6924 against severe hematological adverse events observed when ALRN-6924 was given 24 hours before topotecan in the dose optimization part of the trial, as reported by Aileron earlier this month.

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!

"Following our recent announcement of positive interim data from the Phase 1b dose optimization part of this ongoing Phase 1b/2 study, we are pleased to reach another key milestone in our advancement of ALRN-6924 to potentially transform the treatment paradigm for cancer patients undergoing chemotherapy," said Manuel Aivado, M.D., Ph.D., President & CEO of Aileron Therapeutics.

Dr. Aivado explained, "Chemotherapy remains a critical cornerstone treatment for millions of cancer patients. Unfortunately, in the process of killing cancer cells, chemotherapy inadvertently harms healthy cells, too. This leads to a multitude of common, damaging, severe toxicities. We treat healthy cells ahead of chemotherapy to prevent those toxicities, importantly, without interrupting chemotherapy’s potent onslaught against cancer cells. ALRN-6924 could dramatically improve patients’ quality of life by improving their tolerance to chemotherapy."

ALRN-6924’s novel mechanism of action leverages the innate ability of intracellular p53 protein to induce cell cycle arrest in healthy cells to prevent toxicities driven by chemotherapy’s off-target effects in bone marrow and potentially other tissues and organs. In patients with p53-mutant cancers, which represent approximately 50% of all cancer patients, ALRN-6924 is designed to shield healthy cells from chemotherapy while preserving the susceptibility of cancer cells to chemotherapy.

About the Phase 1b/2 Study

The ongoing Phase 1b/2 study is designed to identify an optimal dose and schedule of ALRN-6924 administration to reduce chemotherapy toxicities such as severe anemia, thrombocytopenia, and neutropenia caused by topotecan in patients with small cell lung cancer. There are two parts to the Phase 1b study: (i) dose optimization and (ii) schedule optimization.

In the dose optimization part, which enrolled 18 patients, ALRN-6924 was administered at three dose levels (0.3, 0.6, and 1.2 mg/kg) 24 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. An expansion cohort of the dose optimization part of the trial at the 0.3 mg/kg dose level is ongoing.

Aileron announced positive interim findings from this part of the trial in June 2020. ALRN-6924 demonstrated a protective effect against severe chemotherapy-induced anemia and thrombocytopenia across all dose levels as compared to historical controls. In addition, patients treated with 0.3 mg/kg ALRN-6924 met the protocol-defined criteria for reduction of NCI CTC Grade 3/4 neutropenia to ≤50% in the first treatment cycle triggering the expansion cohort in up to eight patients.

In the schedule optimization part, ALRN-6924 is being administered at two dose levels (0.3 and 0.6 mg/kg) 6 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. Aileron expects to enroll approximately 20 patients in this part of the study.
"We were highly encouraged by the strong chemoprotective effect of ALRN-6924 seen in the dose optimization part of this study as previously reported, as it reinforces our belief that ALRN-6924 can selectively induce cell cycle arrest to protect cancer patients from the toxic side effects of chemotherapy," said Vojo Vukovic, M.D., Ph.D., Chief Medical Officer of Aileron. "The schedule optimization part of the trial is intended to inform whether ALRN-6924 given six hours before topotecan can further enhance the protective effects we have observed when giving our drug 24 hours before topotecan."

Phase 1b/2 Trial – Next Steps

While enrollment in the 6-hour dosing schedule is underway, Aileron is continuing to enroll patients in the expansion cohort of its 0.3mg/kg dose level using the 24-hour schedule.

As previously reported, the company plans to report topline data from the schedule optimization and final data from the dose optimization parts of the trial in the fourth quarter of 2020. Aileron expects that these results will enable the company to determine a recommended ALRN-6924 dose and schedule for subsequent trials.

Aileron is carefully monitoring the effect of the coronavirus pandemic on its clinical trial sites and the healthcare system, which may impact the future timing of the trial and the company’s planned data announcements.

About ALRN-6924
ALRN-6924 is a first-in-class dual MDM2/MDMX inhibitor that is currently being evaluated in a Phase 1b/2 clinical trial as a chemoprotective agent to protect against chemotherapy-related toxicities.

CRISPR THERAPEUTICS ANNOUNCES PROPOSED PUBLIC OFFERING OF COMMON SHARES

On June 29, 2020 CRISPR Therapeutics (Nasdaq:CRSP), a biopharmaceutical company focused on developing transformative gene-based medicines for serious diseases, reported that it is commencing an underwritten public offering of $325,000,000 of common shares (Press release, CRISPR Therapeutics, JUN 29, 2020, View Source [SID1234563988]). In addition, the underwriters will have a 30-day option to purchase up to an additional $48,750,000 of common shares at the public offering price less the underwriting discount.

Goldman Sachs & Co. LLC, BofA Securities and Jefferies are acting as joint book-running managers for the offering. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering.

The common shares will be offered and sold pursuant to the Company’s previously filed automatically effective shelf registration statement on Form S-3 (File No. 333-227427) filed with the U.S. Securities and Exchange Commission (the "SEC") on September 19, 2018. This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

The offering will be made only by means of a prospectus. A copy of the prospectus supplement relating to the offering will be filed with the SEC and may be obtained, when available, from Goldman Sachs & Co. LLC by mail at 200 West Street, New York, NY 10282, Attention: Prospectus Department, by telephone at (866) 471-2526, or by email at [email protected]; from BofA Securities by mail at NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email at [email protected]; or from Jefferies, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 547-6340, or by email at [email protected].

Cancer Prevention Pharmaceuticals Submits
New Drug Application to the FDA for CPP-1X/sul for Treatment of Familial Adenomatous Polyposis

On June 29, 2020 Cancer Prevention Pharmaceuticals, Inc. (CPP), a private biotech company developing novel therapeutics to prevent cancer and other diseases, reported that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for CPP-1X/sul for treatment of adults with familial adenomatous polyposis (FAP) (Press release, Cancer Prevention Pharmaceuticals, JUN 29, 2020, https://www.canprevent.com/wp-content/uploads/2020/06/NDA-Submission-Press-Release-FINAL-2020-06-29.pdf [SID1234563867]). FAP is a rare genetic disease that if left untreated progresses to colorectal cancer in nearly 100% of patients. The clinical development of CPP-1X/sul was designed to establish this fixed dose combination product as a potential pharmaco-preventive drug treatment specifically for FAP patients.

"The NDA submission for our lead drug candidate, CPP-1X/sul, represents a significant milestone for FAP patients and their families," said CPP CEO Jeff Jacob. "For most FAP patients, current medical practice involves a lifetime of periodic monitoring as well as highly invasive surgical procedures. If approved, CPP-1X/sul could provide an alternative to surgery for many patients, significantly improving their quality of life."

The FDA’s accelerated approval process allows the agency to approve drugs which address a serious or life-threatening condition based on an intermediate or surrogate endpoint that is likely to predict a clinical long-term benefit. The FDA takes into account such factors as the severity, rarity, or the lack of effective current treatments. The designation has been frequently applied to cancer drugs.

In addition, CPP-1X/sul received an orphan drug designation from the FDA. Among the benefits are eligibility for seven years of market exclusivity upon approval of a drug and tax credits for various costs of clinical testing.

CPP also recently submitted a Marketing Authorization Application (MAA) with the European Union (EU) for CPP-1X/sul for the same indication. The drug received an orphan medicinal product designation for FAP following a favorable assessment provided by the European Medicines Agency’s Committee for Orphan Medicinal Products.

About CPP-1X/sul
CPP-1X/sul is a combination of CPP-1X (eflornithine) and sulindac (CPP-1X/sul). In a clinical trial in patients with large bowel polyps, the CPP-1X/sul combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Based on the close biologic similarities with FAP, a Phase 3 pivotal trial compared this same combination to each drug alone (CPP FAP-310).

"With up to four years of treatment, the combination appears to greatly delay the need for major surgeries in the colon, rectum or surgical pouch. We hope that this new drug regimen will soon be available as an adjunct in the management of FAP patients facing large bowel surgery," said Dr. Alfred Cohen, Chief Medical Officer of CPP.

The CPP FAP-310 trial enrolled 171 FAP patients at 17 research institutes in the U.S., Canada, and Europe. It was the largest ever prospective, controlled study performed in FAP and treated patients for up to 48 months, much longer than any other clinical trial in this population. The study was designed to determine if CPP-1X/sul is superior to sulindac or eflornithine as single agents in delaying time to the first occurrence of any FAP-related event, such as surgical removal of the colon, rectum, surgical pouch, duodenum and/or high-risk adenomas. The trial design included FAP patients with varying lower and upper GI disease. CPP-1X/sul did not demonstrate statistical significance in outperforming the single agents in the overall population; however, further analysis of the data showed key differential effects of the agents in the lower vs upper GI anatomy. Focusing on lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), the data showed statistically significant benefit for CPP-1X/sul vs both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. Also, the safety profile of the combination did not significantly differ from that already known for the single agents to support the overall safety assessment of the fixed combination product for long-term therapeutic use.

OmniSeq Offers Differentiating Platform to Clinically Detect Rare Genetic Alterations to Identify Patients Eligible for New, Targeted Therapy for Lung and Thyroid Cancer

On June 29, 2020 OmniSeq, an innovator in next generation sequencing (NGS) in oncology, reported the benefits of its OmniSeq Advance comprehensive genomic and immune profiling assay to detect the presence of rare alterations in the RET gene in the tumors of some patients with non-small cell lung cancer (NSCLC) and thyroid cancer (Press release, OmniSeq, JUN 29, 2020, View Source [SID1234561571]). Those patients eligible for treatment with Eli Lilly and Company’s recently FDA-approved selective RET kinase inhibitor Retevmo* (selpercatinib).

Retevmo is the first FDA-approved therapy specifically for cancer patients with fusions or mutations in the RET (rearranged during transfection) gene. OmniSeq Advance delivers the distinct advantage of using two technologies; RNA-sequencing for RET fusions and DNA-sequencing for RET mutations to provide optimal, comprehensive testing for Retevmo. OmniSeq Advance was one of the tests that could qualify a patient for enrollment to the LIBRETTO-001 Retevmo (selpercatinib) clinical trial.

The National Comprehensive Cancer Network (NCCN) recommends for NSCLC that when feasible, testing be performed via a broad, panel-based approach, most typically performed by next generation sequencing. For patients who, in broad panel testing don’t have identifiable driver oncogenes (especially in never smokers), consider RNA-based NGS if not already performed, to maximize detection of fusion events.

"OmniSeq Advance offers significant advantages for detecting RET fusions by RNA-sequencing as opposed to DNA-only sequencing," stated OmniSeq’s Chief Medical Officer, Roger Klein, MD, JD, FACP. "OmniSeq’s proprietary sample preparation methodologies also allow for minimal tumor tissue input, a critical factor for ensuring NSCLC patient testing can be completed with frequently limited biopsy material available."

OmniSeq’s NGS-based assays provide comprehensive genomic and immune profiling from RNA and DNA to enable oncologists to select the most appropriate therapies or clinical trials for each patient. OmniSeq’s suite of clinical diagnostic tests are offered exclusively by LabCorp to U.S.-based physicians through its Integrated Oncology specialty laboratory and to global biopharmaceutical customers through Covance, LabCorp’s drug development business. OmniSeq Advance is approved by New York State’s Clinical Laboratory Evaluation Program.

Retevmo is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer, of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trial(s). There is currently no FDA-approved companion diagnostic for Retevmo.

2 early-stage biotechs gun for $175M as IPO waters remain warm

On June 29, 2020 ALX Oncology Holdings, a next-gen cancer biotech reported that that launched in 2015 seeking a $100 million IPO to add to its recent $105 million funding round (Press release, FierceBiotech, JUN 29, 2020, View Source [SID1234561570]).

The Dublin- and California-based biotech has so far had a good year and, back in February, just after its series C round, grabbed an FDA speedy tag for its leading candidate ALX148 for the first-line treatment of patients with head and neck squamous cell carcinoma and for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction carcinoma.

WEBINAR
De-risking the Development of Biotherapeutics Using Early Stage In Vitro Expression and Genetic Characterisation Tools
There is a high attrition rate during the development of biotherapeutics impacting the high cost of development. Early identification of the preferred expression host for manufacturing, along with lead candidate screening and material supply can help to reduce both attrition rates and cost.
REGISTER NOW
CD47 myeloid checkpoint inhibitor ALX148 is now in line for phase 2 trials in combination with other anti-cancer therapies.

Multiple drug developers have gone after CD47 since evidence of its role in the interactions between cancer cells and the immune system became clear. The evidence suggested tumors evade immune attacks by upregulating CD47, leading researchers to posit that blocking the signal will expose cancer cells to a full-force offensive.

However, efforts to realize the therapeutic potential of anti-CD47 antibodies have been undermined by hematological adverse events stemming from the fact the target is found on host cells such as red blood cells.

ALX, formerly known as Alexo Therapeutics, thinks fusion protein ALX148 has a better risk-benefit profile than its rivals and has persuaded investors to buy into that idea.

Some of its more recent data were from patients with relapsed or refractory non-Hodgkin lymphoma (NHL) who received ALX148 in combination with rituximab. Among the 21 evaluable patients, ALX saw an objective response rate of 43% and a median progression-free survival of 7.3 months. As importantly, the drug appeared to be relatively safe and well tolerated.

The phase 1 trial that generated the lymphoma data is continuing, with other arms of the study testing the CD47 prospect in combination with Herceptin and Keytruda in solid tumor patients. But, with ALX148 coming through its first test in NHL, ALX also has plans to take the candidate deeper into the clinic.

The biotech said in a Securities and Exchange Commission (SEC) filing that it now also plans to advance ALX148 into a phase 1b/2 trial in combination with Vidaza (azacitidine) for myelodysplastic syndromes by the end of 2020 and a phase 1b/2 trial in combination with standard-of-care agents for acute myeloid leukemia in 2021.

It plans to list on the Nasdaq under the symbol "ALXO."

The second IPO attempt is a $75 million effort from autoimmune biotech Pandion Therapeutics. Since it uncloaked two years ago, Pandion has teamed up with Astellas on bispecific drugs for Type 1 diabetes and has pushed its lead program into the clinic.

Back in April, it raised $80 million to test that treatment in patients with ulcerative colitis and move a second program into phase 1.

Cambridge, Massachusetts-based Pandion set up shop with its so-called TALON platform to create better treatments for autoimmune conditions, in which the immune system "forgets what the self is" and attacks its own tissues and organs. It aims to replace old-school systemic immunosuppression—which can lead to side effects like an increased risk of infection or cancer—as well as newer anti-cytokine antibodies, which have improved care for some patients but don’t work for all autoimmune diseases.

Its lead asset, PT101, is a combination of an interleukin-2 mutein effector module with a protein backbone and is designed to selectively expand regulatory T cells systemically without activating proinflammatory cells, such as conventional T cells and natural killer cells.

"We are initially developing PT101 for the treatment of patients with moderate-to-severe ulcerative colitis, or UC, and are currently conducting a Phase 1a clinical trial of PT101 in healthy volunteers, with final data expected in the first half of 2021," the biotech said in its SEC-1 filing.

Using its TALON platform, it added it would also "continue to develop and expand our library of effector and tether modules as part of our early stage research and discovery pipeline."