On June 29, 2020 Boryung Pharmaceutical is developing BR101801 (project name BR2002) is an anti-cancer drug which simultaneously inhibits PI3K (γ/δ) and DNA-PK, showed its potential as a treatment in various solid cancer models as well as in blood cancer (Press release, Boryung Pharmaceutical, JUN 29, 2020, View Source [SID1234644864]).

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Boryung Pharmaceutical unveiled some of the pre-clinical trial results of BR101801 at the annual conference of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), which was held online on the 22nd (local time).

PI3K (phosphoinositide3-kinase) is an enzyme that regulates intracellular signal transduction process and regulates multiple functions such as cell growth, proliferation and differentiation, migration, and survival. As an enzyme that recognizes and repairs DNA damage in cells, DNA-PK helps cancer cells survive despite of DNA damage.

BR101801, solely developed by Boryung Pharmaceutical, is a target anti-cancer agent and cancer immunotherapy agent that simultaneously inhibits PI3K and DNA-PK. In this AACR (Free AACR Whitepaper), Boryung Pharmaceutical released total of 3 posters of which are related to cancer cell death of BR101801: efficacy in monotherapy and combined therapy, efficacy as an cancer immunotherapy drug, ability to inhibit repair factor of cancer cell damage.

Boryung Pharmaceutical not only uses BR101801 alone but also BR101801+ anti PD-1, BR101801+ anti PD-L1, BR101801+ OX40, BR101801+ Doxorubicin in various animal models such as liver cancer, breast cancer, lung cancer and colon cancer models. As a result of combination therapy, efficacy of BR101801 in terms of survival rate and tumor size was confirmed as compared with the control group.

Boryung Pharmaceutical has also conducted a mono and combined efficacy study of BR101801 on cancer cell deaths from peripheral blood mononuclear cells (human PBMCs). Gilead’s Zydelig (Idelalisib), Verastem’s Copiktra (Duvelisib) and other drugs that have been approved as PI3K inhibitors to date have been set as a control group for comparative studies. As a result, it was confirmed that BR101801 showed superior efficacy in killing cancer cells and controlling c-Myc (tumor-inducing gene) compared to the controls from 52 hematological cancer cell lines.

Especially when BR101801 alone is administered, Treg (regulatory T cells) and MDSC (bone marrow-derived suppressor cells), which are immunosuppressive cells, are decreased, and CD8+, which is an immune cell that kills cancer cells, is increased. It has confirmed its effects of a cancer immunotherapy agent. Also, it showed the effect of inhibiting DNA-PK, which is an enzyme involved in recognizing DNA damage in cancer cells and involved in repair, and showed the effect of killing cancer cells.

The researcher team said, "BR101801 has been shown to have the effect of killing cancer cells not only in blood cancer but also in various solid cancers when co-administered with cytotoxic anti-cancer drug or through the radiation."

Boryung Pharmaceutical said BR101801 has been currently undergoing 1st clinical phase for the indication of non-Hochkin’s lymphoma, a type of blood cancer, simultaneously in Korea and in the U.S. since this March.

On June 29, 2020 PharmEnable, a Cambridge-based drug discovery company using advanced medicinal chemistry and AI-enabled approaches to design the next generation of highly complex and specific drug candidate molecules, reported it has closed a £1.8 million seed financing to support its transition into a drug development company (Press release, PharmEnable, JUN 29, 2020, View Source [SID1234641051]). It aims to develop new treatments for conditions with significant unmet clinical need, by designing highly complex molecules for addressing challenging biological targets. The round, which was significantly over-subscribed, was led by Cambridge Enterprise, the commercialisation arm of the University of Cambridge, as well as the University of Cambridge Enterprise Fund VI, managed by Parkwalk Advisors. It also attracted support from a wealth of angel investors and notable life science funds, including Jonathan Milner, serial entrepreneur and founder of Abcam; Andy Richards, Cambridge-based entrepreneur and investor; David Ford, Oxford-based life sciences angel investor; the family office of Paul Forster, co-founder of Indeed.com; Ian Tomlinson, chairman of several bio-incubators, entrepreneur and co- founder of Domantis; KQ Labs at the Francis Crick Institute; Martlet Capital, a Cambridge-based investor with a growing portfolio of innovative life science companies; the fast-growing o2h ventures Human Health EIS fund; and Wren Capital, the established London-based angel investor in science, engineering and software businesses. A spin-out from the University of Cambridge in 2016, and financed to date by its founders and service-based revenues, PharmEnable will use the funding to evolve its business model and invest in a pipeline of drug discovery programmes across a number of disease areas including cancer and neurodegenerative disease. Additionally, PharmEnable will continue to engage in strategic partnerships with pharma, innovative biotechs and academia. PharmEnable is led by co-founder and CEO Dr Hannah Sore. It has attracted an experienced Board and management team including Dr Jane Dancer, previously of F-star, who joined recently as the new Board Chair. The financing has enabled PharmEnable to expand its scientific team including Dr David Vidal as Director of Technology, with further expansion, including the addition of a Director of Drug Discovery planned for Q3 2020. The PharmEnable platform technology can predict improved small molecule hits to targets across a range of disease areas. Its approach focuses on exploring and mapping the possible chemical universe and designing novel small molecules that are highly complex with shapes similar to those found in nature. This approach can identify hits with improved specificity compared with traditional screening methods, and allows PharmEnable to take on particularly challenging biological targets, such as protein-protein interactions and epitranscriptomic modifications that have been undruggable by existing approaches. Its solution consists of two elements: ChemUniverse a diversity-focused virtual database of chemically diverse molecules; and ChemSeek, a suite of gold standard AI-enabled tools for finding drug target matches from structure and ligand data.

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Commenting on the financing, CEO of PharmEnable Dr. Hannah Sore said:

"We are pleased to welcome on board our new investors and appreciate their confidence in our business. Our aim is to replicate the specificity of biologics in the powerful and scalable form of a small molecule, to treat devastating diseases where there are currently no treatment options. We have proven the strength of our platform in tapping unexplored parts of the chemical universe to find novel and specific hits for currently undruggable targets, and are excited to now be able to invest in our own pipeline of drug discovery programmes, as well as to develop further strategic partnerships."

Dr Christine Martin, Head of Life Science Investment at Cambridge Enterprise said:

"Cambridge Enterprise is really pleased to be investing in this exciting opportunity. To have closed the round during these last few months, and to have attracted such a strong investor syndicate, is a testament to the potential of the AI-enabled platform that PharmEnable has built. We are pleased to support the Company in its transition to in-house drug discovery. We believe the company will have significant impact through addressing undruggable therapeutic targets."

Following the investment, Dr Christine Martin, Head of Life Science Investment at Cambridge Enterprise and Peter McPartland, Investment Director of Martlet Capital and representative for all other investors, join the board of directors of PharmEnable, alongside Dr Jane Dancer (independent Chair), Dr Hannah Sore (CEO) Dr Natalia Mateu (CSO) and Gaynor Fryers (independent NED). David Ford also serves as a Board Observer for the entrepreneurs/angel investors.

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.

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"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.

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.

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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].

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.

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"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.