On March 5, 2020 Idera Pharmaceuticals, Inc. ("Idera" or "the company") (NASDAQ: IDRA) reported completion of patient enrollment into ILLUMINATE-301, its registrational trial of tilsotolimod in combination with ipilimumab in patients with anti-PD-1 refractory advanced melanoma (Press release, Idera Pharmaceuticals, MAR 5, 2020, View Source [SID1234555198]). The company expects to announce top-line overall response rate (ORR) and other preliminary data from ILLUMINATE-301 in Q1 2021.

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"We are making outstanding progress in moving toward our goal of delivering tilsotolimod to the market in our lead indication for anti-PD-1 refractory advanced melanoma patients," stated Vincent Milano, Idera’s Chief Executive Officer. "We achieved this critical milestone earlier than anticipated, which we believe is truly a testament to the high unmet need facing these patients."

Added Elizabeth Tarka, M.D., Idera’s Chief Medical Officer, "We believe tilsotolimod in combination with ipilimumab may be an important new therapeutic option for these patients, and we are incredibly grateful to them, their families, and our investigators for their participation in ILLUMINATE-301. We look forward to sharing the results of this exciting trial soon."

ILLUMINATE-301 is a randomized, phase 3 trial comparing the effectiveness of intratumoral tilsotolimod in combination with ipilimumab with ipilimumab alone in patients with anti-PD-1 refractory advanced melanoma, with a primary endpoint family of ORR per RECIST v1.1 and overall survival (OS). Key secondary endpoints include durable response rate, time to response, progression-free survival, patient-reported outcomes, and safety. ILLUMINATE-301 enrolled 481 patients across 80 sites in 11 countries.

About Anti-PD-1 Refractory Advanced Melanoma

Melanoma is a cancer that begins in a type of skin cell called melanocytes. While melanoma is one of the least common types of skin cancer, it has a poor prognosis when not detected and treated early. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread, or metastasized, beyond the skin to other parts of the body. According to the American Cancer Society, approximately 100,000 people in the US will be diagnosed with invasive melanoma this year. In recent years, pioneering immunotherapies known as checkpoint inhibitors (CPIs) have changed the treatment of advanced melanoma and have become the standard of care, with anti-PD-1 agents being the most commonly used immunotherapy in the first-line setting. These agents work by increasing the ability of the body’s immune system to help detect and fight cancer cells. However, due to primary or acquired resistance mechanisms that exclude or inhibit anti-tumor immune cells, as many as 60% of patients do not benefit from this type of therapy, and up to one-third of initial responders develop resistance to the therapy and ultimately experience disease progression. Today, these refractory patients are left with few options for further treatment, paving the way for novel investigational therapies such as tilsotolimod.

About Tilsotolimod (IMO-2125)

Tilsotolimod is an investigational, synthetic Toll-like receptor 9 agonist. Intratumoral injection of tilsotolimod has been shown to promote both innate (Type-I IFN, antigen presentation) and adaptive (T cells) immune activation. Tumors with an active immune response appear to respond better to CPIs than those that exclude or inhibit anti-tumor immune cells. Thus, tilsotolimod in combination with CPIs may cause regression of locally injected and distant tumor lesions and increase the number of patients who benefit from immunotherapy.

Tilsotolimod has received both Fast Track designation and Orphan Drug designation from the FDA and is being evaluated in multiple tumor types and in combination with multiple checkpoint inhibitors. For more information on tilsotolimod trials, please visit www.clinicaltrials.gov.

On March 5, 2020 Arbutus Biopharma Corporation (Nasdaq: ABUS), a Hepatitis B Virus (HBV) therapeutic solutions company, reported its fourth quarter and year end 2019 financial results, confirms 2020 corporate objectives and provides pipeline update (Press release, Arbutus Biopharma, MAR 5, 2020, View Source [SID1234555197]).

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"Arbutus is focused on developing a portfolio of medicines with different mechanisms of action that we believe could provide a functional cure for people with chronic hepatitis B," said William Collier, Arbutus’ President and Chief Executive Officer. "Our key objectives for 2020 are to complete and report results from the Phase 1a/b clinical trial of AB-729, our proprietary subcutaneous RNAi agent, and rapidly advance our next-generation oral capsid inhibitor, AB-836, through IND-enabling studies by year end.

Mr. Collier added, "We remain on track to announce preliminary safety and efficacy results from multiple single-dose cohorts in the Phase 1a/1b clinical trial for AB-729 later this month."

Pipeline Update

AB-729

AB-729 is an RNA interference (RNAi) therapeutic targeted to hepatocytes using Arbutus’ novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology that enables subcutaneous delivery. AB-729 inhibits viral replication and reduces all HBV antigens, including hepatitis B surface antigen (HBsAg), in preclinical models. Reducing HBsAg is thought to be a key prerequisite to enable reawakening of a patient’s immune system to respond to the virus.

Arbutus is currently conducting a single- and multiple-dose Phase 1a/1b clinical trial for AB-729 to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of AB-729 in healthy volunteers and in subjects with chronic hepatitis B (CHB) infection.

Preliminary safety data in single-dose cohorts of healthy subjects and safety and efficacy data in single-dose cohorts of subjects with CHB infection are expected later this month. Additional single-dose data and preliminary multi-dose data are expected in the second half of 2020.

AB-836

AB-836 is an oral HBV capsid inhibitor. HBV core protein assembles into a capsid structure, which is required for viral replication. The current standard-of-care therapy for HBV, primarily nucleoside analogues that work by inhibiting the viral polymerase, significantly reduce virus replication, but not completely. Capsid inhibitors inhibit replication by preventing the assembly of functional viral capsids. They also have been shown to inhibit the uncoating step of the viral life cycle thus reducing the formation of new covalently closed circular DNA (cccDNA), the viral reservoir which resides in the cell nucleus.

In January 2020, Arbutus selected AB-836 as its next-generation oral capsid inhibitor. AB-836 is a novel chemical series differentiated from Arbutus’ previously discontinued capsid inhibitor candidate, AB-506, and other competitor compounds in the capsid inhibitor space. AB-836 has the potential for increased potency and an enhanced resistance profile compared to AB-506, our previous generation capsid inhibitor that was discontinued in October 2019. Arbutus anticipates completing IND-enabling studies by the end of 2020.

Early R&D Programs

Arbutus continues a focused discovery effort on follow-on compounds for its current HBV pipeline, including the development of oral RNA-destabilizers that have shown compelling anti-viral effects in multiple HBV preclinical models. Arbutus is now focused on advancing a next-generation oral HBV specific RNA-destabilizer with chemical scaffolds distinct from AB-452 through lead optimization. Arbutus also has compounds in lead optimization that are potentially capable of reawakening patients’ HBV-specific immune response by inhibiting PD-L1.

Cash Position and 2020 Cash Guidance

Arbutus ended the year with $90.8 million in cash, cash equivalents and short-term investments which the Company believes is sufficient to fund operations into mid-2021. Arbutus expects to utilize between $54 to $58 million of cash and investments to fund operations in 2020.

Financial Results

Cash, Cash Equivalents and Investments

Arbutus had cash, cash equivalents and short-term investments totaling $90.8 million as of December 31, 2019, as compared to $124.6 million as of December 31, 2018. The decreased cash balance was due primarily to the $71.0 million used in operating activities during the year ended December 31, 2019, partially offset by $18.5 million in net proceeds from the sale of Arbutus’ portion of a royalty entitlement on net sales of Alnylam Pharmaceuticals, Inc.’s ONPATTROTM (Partisiran) in the third quarter of 2019 and $18.6 million of net proceeds from the issuance of shares under Arbutus’ ATM program. Included in the $71.0 million used in operating activities is a $5.9 million payment in the third quarter of 2019 for an award rendered in an arbitration proceeding with the University of British Columbia. Subsequent to year end, Arbutus has received an additional $12.3 million of net proceeds from the issuance of shares under Arbutus’ ATM program during the first quarter of 2020 through March 4, 2020.

Net Loss

Net loss attributable to common shares for the year ended December 31, 2019, including non-cash charges of $43.8 million related to the impairment of an in-process research and development ("IPR&D") intangible asset and $22.5 million for the impairment of goodwill described further below, was $164.9 million ($2.89 basic and diluted loss per common share) as compared to $67.2 million ($1.21 basic and diluted loss per common share) in 2018. Net loss attributable to common shares also included non-cash expense for the accrual of coupon on the Company’s convertible preferred shares of $11.1 million in 2019 and $10.1 million in 2018, as well as non-cash equity losses associated with our investment in Genevant Sciences Ltd.’s ("Genevant") of $22.5 million in 2019 and non-cash equity gains of $19.3 million in 2018. Genevant is a company launched with Roivant Sciences Ltd., Arbutus largest shareholder, in April 2018.

ONPATTRO Royalty Entitlement

Arbutus has a royalty entitlement on global net sales of ONPATTRO (Patisiran) for the lipid nanoparticle delivery (LNP) technology licensed by Arbutus to Alnylam for this product. ONPATTRO is an RNAi therapeutic for the treatment of hereditary ATTR (hATTR) amyloidosis that has been approved by the U.S. Food and Drug Administration and the European Medicines Agency. In July 2019, Arbutus sold this royalty entitlement to OCM IP Healthcare Portfolio LP, an affiliate of the Ontario Municipal Employees Retirement System (collectively, OMERS), effective as of January 1, 2019, for $20 million in gross proceeds before advisory fees. OMERS will retain this royalty entitlement until it has received $30 million in royalties, at which point 100% of this royalty entitlement will revert to Arbutus. OMERS has assumed the risk of collecting up to $30 million of future royalty payments from Alnylam and Arbutus is not obligated to reimburse OMERS if they fail to collect any such future royalties. Arbutus recognized the $20 million of gross proceeds from this transaction as a liability, net of transaction costs. The Company is amortizing the liability to non-cash interest expense and will continue to recognize the royalty revenue that Alnylam pays to OMERS as non-cash royalty revenue.

In addition to the royalty entitlement from the Alnylam LNP license agreement, Arbutus is also receiving a second, lower royalty entitlement on global net sales of ONPATTRO originating from a settlement agreement and subsequent license agreement with Acuitas Therapeutics. The royalty entitlement from Acuitas has been retained by Arbutus and is not part of the royalty entitlement sale to OMERS.

Operating Expenses

Research and development expenses were $57.6 million for the year ended December 31, 2019 compared to $57.9 million in 2018. Research and development expenses for the year ended December 31, 2019 included costs associated with the Company’s Phase 1a/1b clinical trial for its RNAi agent (AB-729), Phase 1a/1b clinical trial for its oral capsid inhibitor (AB-506), which was discontinued in October 2019, and toxicology studies for its HBV RNA Destabilizer (AB-452), which was discontinued in February 2020. General and administrative expenses were $17.7 million in 2019 compared to $16.0 million in 2018. The increase in general and administrative expenses was due primarily to severance related to our former President and Chief Executive Officer’s departure from the Company in June 2019, partially offset by a decrease in professional fees. In accordance with the terms of his legacy employment agreement, our former President and Chief Executive Officer received $2.3 million in cash severance and the Company recognized $1.1 million of non-cash stock-based compensation expense for accelerated vesting of his stock options.

Additionally, the Company recorded a charge of $6.3 million in 2019 related to an arbitration award from the Company’s arbitration with the University of British Columbia.

Impairment of IPR&D Intangible Assets and Goodwill

The Company has historically carried IPR&D and goodwill from its acquisition of technologies and business combination as assets. All acquired IPR&D intangible assets relate to the Company’s cccDNA program. During the year ended December 31, 2019, the Company recorded a $43.8 million non-cash impairment expense to reduce the carrying value of its IPR&D intangible assets to zero. The Company also recognized a corresponding income tax benefit of $12.7 million related to the decrease in its deferred tax liability associated with the IPR&D intangible assets. The impairment was due to an indefinite delay in further development of the Company’s cccDNA program while the Company focuses on its other development programs.

Goodwill represents the excess of purchase price over the value assigned to the net tangible and identifiable intangible assets in connection with the business combination that formed Arbutus. The Company assessed changes in circumstances to determine if it was more likely than not that the fair value of the Company was below its carrying amount. Due to a sustained decrease in the Company’s share price during the year, the Company’s market capitalization was reduced below the book value of its net assets and the Company concluded that its fair value was below its carrying amount by an amount in excess of the carrying value of the goodwill. As a result, during the third quarter of 2019,

3

the Company recorded a $22.5 million non-cash impairment expense to reduce the carrying value of its goodwill asset to zero.

Outstanding Shares

The Company had 64,780,314 common shares issued and outstanding as of December 31, 2019. In addition, the Company had approximately 8.6 million stock options outstanding and 1.164 million convertible preferred shares outstanding, which (including the annual 8.75% coupon) will be mandatorily convertible into approximately 23 million common shares on October 18, 2021.

Conference Call Today

Arbutus will hold a conference call and webcast today, Thursday, March 5, 2020 at 8:45 AM Eastern Time to provide a corporate update. You can access a live webcast of the call through the Investors section of Arbutus’ website at www.arbutusbio.com. Alternatively, you can dial (866) 393-1607 or (914) 495-8556 and reference conference ID 5084457.

An archived webcast will be available on the Arbutus website after the event. Alternatively, you may access a replay of the conference call by calling (855) 859-2056 or (404) 537-3406, and reference conference ID 5084457.

On March 5, 2020 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the fourth quarter and full year ended December 31, 2019, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAR 5, 2020, View Source [SID1234555195]).

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"2020 is off to a strong start, with NDAs accepted and approvals lined up later this year in the U.S. and Japan, and continued progress with our oral Factor D program as we approach proof of concept data in PNH patients in the second quarter of the year," said Jon Stonehouse, president and chief executive officer of BioCryst.

"We are hearing increasing excitement from both HAE patients and physicians about the availability of an oral option to manage their disease, and we are attracting outstanding commercial talent to bring this new medicine to patients," Stonehouse added.

Upcoming Key Milestones

HAE Program – Berotralstat (BCX7353)

Submit Marketing Authorization Application (MAA) for oral, once-daily berotralstat for the prevention of hereditary angioedema (HAE) attacks with the European Medicines Administration (EMA) (Q1 2020)

Approval and launch of oral, once-daily berotralstat in Japan (2H 2020)

Approval and launch of oral, once-daily berotralstat in U.S. (December 3, 2020 PDUFA date)
Complement Oral Factor D Inhibitor Program – BCX9930

Report data from a proof of concept study in paroxysmal nocturnal hemoglobinuria (PNH) patients receiving oral BCX9930 (2Q 2020)
ALK-2 Inhibitor Program – BCX9250

Report data from Phase 1 clinical trial of BCX9250, an oral ALK-2 kinase inhibitor for treatment of fibrodysplasia ossificans progressiva (FOP), in healthy subjects (2H 2020)
Coronavirus Antiviral Update – Galidesivir (BCX4430)
Galidesivir is a broad-spectrum antiviral currently being developed in a Phase 2 clinical trial (Yellow Fever) under contracts with the National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of Health and Human Services (HHS).

Galidesivir has been shown to be active against more than 20 RNA viruses in nine different families, including coronaviruses. In Phase 1 trials in healthy volunteers, galidesivir was generally safe and well tolerated.

The company is in active dialogue with relevant U.S. public health authorities as they assess potential approaches to treat and prevent COVID-19, and whether galidesivir could be useful.

Recent Corporate Developments

On March 5, 2020, the company announced it had dosed its first PNH patients in a proof of concept study with its oral Factor D inhibitor, BCX9930.

On March 3, 2020, the company announced it will present at the Barclays Global Healthcare Conference in Miami Beach, Florida on Tuesday, March 10, 2020. The company’s presentation time has been changed to 8:30 a.m. ET that day.

On February 27, 2020, the company announced it will present abstracts with new data on oral, once-daily berotralstat (BCX7353) at the upcoming annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) March 13-16 in Philadelphia.

On February 25, 2020 the company announced the appointment of former Pfizer CFO, Alan G. Levin, to its Board of Directors.

On February 18, 2020, the company announced that the U.S. Food and Drug Administration (FDA) had accepted and filed its new drug application (NDA) for the approval of oral, once-daily berotralstat (BCX7353) for the prevention of hereditary angioedema (HAE) attacks. The Prescription Drug User Fee Act (PDUFA) date for the NDA is December 3, 2020. In the NDA filing acceptance letter, the FDA stated that they are not currently planning to hold an advisory committee meeting to discuss the NDA.

On February 3, 2020, the company announced that it had submitted a new drug application (JNDA) to the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for approval of oral, once-daily berotralstat for the prophylactic treatment of HAE.

On January 15, 2020 the company announced the appointments of Charles Gayer as chief commercial officer and Allen Hodge as vice president and general manager for the United States.

On January 12, 2020, the company announced that the APeX-J trial in Japan met its primary endpoint (p=0.003) for prevention of HAE attacks, and berotralstat was safe and generally well-tolerated.

On December 11, 2019, the company announced it had submitted a new drug application to the FDA for approval of oral, once-daily berotralstat (BCX7353) for the prevention of HAE attacks.

On November 18, 2019, the company announced it had completed a public offering of common stock and received gross proceeds of approximately $63.3 million. In addition, the company completed a pre-funded warrants transaction on November 21, 2019 that provided gross proceeds of $19.9 million.
Fourth Quarter 2019 Financial Results

For the three months ended December 31, 2019, total revenues were $39.7 million, compared to $2.7 million in the fourth quarter of 2018. The increase was primarily due to the recognition of $20.1 million of the $22.0 million upfront payment from Torii for commercialization rights in Japan for berotralstat for the prevention of HAE attacks, and $13.9 million of RAPIVAB (peramivir injection) product sales under our procurement contract with the Centers for Disease Control.

Research and development (R&D) expenses for the fourth quarter of 2019 increased to $26.8 million from $23.4 million in the fourth quarter of 2018, primarily due to increased spending on the company’s complement-mediated diseases program and other preclinical development initiatives.

Selling, general and administrative (SG&A) expenses for the fourth quarter of 2019 increased to $10.5 million, compared to $4.5 million in the fourth quarter of 2018. The increase was primarily due to increased spending on commercial activities and medical affairs to support the U.S. commercial launch of berotralstat in 2020 and, to a lesser extent, legal expenses associated with our ongoing arbitration.

Interest expense was $3.1 million in the fourth quarter of 2019, compared to $2.4 million in the fourth quarter of 2018 and was associated with an increase in the outstanding balance of the company’s secured credit facility in February 2019 and increased interest expense associated with the company’s non-recourse notes payable.

Net loss for the fourth quarter of 2019 was $2.6 million, or $0.02 per share, compared to a net loss of $27.4 million, or $0.25 per share, for the fourth quarter of 2018.

Cash, cash equivalents and investments totaled $137.8 million at December 31, 2019, and reflect an increase from $128.4 million at December 31, 2018. Cash and investments reflect the proceeds from a November 2019 equity offering and a prefunded warrants transaction, as well as a $22.0 million upfront payment from Torii, offset by normal operating expenses. Net proceeds from these transactions yielded just over $100 million in capital in the fourth quarter and provide the company sufficient capital to fund the launch of berotralstat in the United States as well as its other planned operations through 2020. Operating cash use for the fourth quarter of 2019 was $33.5 million, and for the full year of 2019 was $111.4 million.

Full Year 2019 Financial Results

For the full year ended December 31, 2019, total revenues were $48.8 million, compared to $20.7 million in the full year ended December 31, 2018. The increase was primarily due to the recognition of $20.1 million of the $22.0 million upfront payment from Torii, $13.9 of RAPIVAB product sales under our procurement contract and $3.7 million of peramivir product sales to our licensing partners. The increase in revenues was partially offset by the recognition of $12.0 million of peramivir milestones recognized in 2018 that did not recur in 2019.

R&D expenses in 2019 increased to $107.1 million from $84.9 million in 2018, primarily due to increased spending on the company’s complement-mediated diseases program and other preclinical development initiatives.

SG&A expenses in 2019 increased to $37.1 million, compared to $29.5 million in 2018. The increase was primarily due to increased spending on commercial activities and medical affairs to support the U.S. commercial launch of berotralstat in 2020. The increased commercial and medical affairs costs were partially offset by the non-recurring merger-related costs associated with the company’s terminated merger with Idera and a $4.9 million reserve for collectability of the EMA approval milestone of peramivir.

Interest expense was $11.9 million in 2019, compared to $9.2 million in 2018. The increase was associated with an increase in the outstanding balance of the company’s secured credit facility in February 2019 and increased interest expense associated with the company’s non-recourse notes payable.

Net loss for 2019 was $108.9 million, or $0.94 per share, compared to a net loss of $101.3 million, or $0.98 per share, for 2018.

Financial Outlook for 2020

BioCryst expects full year 2020 net operating cash use to be in the range of $125 to $150 million, and its operating expenses to be in the range of $135 to $160 million. The company’s operating expense range excludes equity-based compensation expense due to the difficulty in reliably projecting this expense, as it is impacted by the volatility and price of the company’s stock, as well as by the vesting of the company’s outstanding performance-based stock options.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 7351587. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 7351587.

On March 5, 2020 Sysmex Corporation (HQ: Kobe, Japan; Chairman and CEO: Hisashi Ietsugu) reported notice that Dr. Yu Sunakawa, Associate Professor in the Department of Clinical Oncology at the St. Marianna University School of Medicine, presented his research findings at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium 2020 (ASCO-GI 2020), held in San Francisco, California, the United States, from January 23 to 25, 2020 (Press release, Sysmex, MAR 5, 2020, View Source [SID1234555193]). This research involved examining the utility of RAS gene1 mutation testing for colorectal cancer with liquid biopsy2 using BEAMing technology3 (OncoBEAMTM RAS CRC Kit) to help guide treatment decisions for the re-challenge of anti-EGFR monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC).

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This research involved collaborative biomarker studies (JACCRO CC-084 and CC-09AR5) conducted in cooperation with Sysmex and the Japan Clinical Cancer Research Organization (Location: Tokyo, Japan; Director: Dr. Fumimaro Takaku; "JACCRO").

The overexpression of epidermal growth factor receptors (EGFR) on the surface of colorectal cancer cells is known to promote their cellular proliferation. Numerous studies have shown that anti-EGFR monoclonal antibody drugs are effective in preventing the proliferation of these cancer cells; however, this therapy is not effective in patients whose colorectal tumors harbor RAS mutations. Accordingly, decisions on the administration of anti-EGFR monoclonal antibody drugs are usually made by assessing RAS gene mutations using resected tissues.

In recent years, clinical studies have actively investigated re-challenge of mCRC patients with antiEGFR therapy in an effort to improve the prognosis of patients who had previously responded to 1st-line anti-EGFR therapy treatment, but whose disease progressed during subsequent courses of therapy in which anti-EGFR drugs were eliminated. In the process, it was reported that no clinical benefit by the re-challenge of anti-EGFR monoclonal antibody drugs on patients determined to have wild-type RAS genes at the time of initial administration of anti-EGFR monoclonal antibody drugs might be due to the emergence of RAS mutations during anti-EGFR therapy (Source: JAMA Oncol. 2019;5(3):343-350).

Sysmex and JACCRO’s objective of this clinical research (JACCRO CC-08/09AR studies: retrospective6 study), was to examine a possible relationship between clinical outcomes of the antiEGFR re-challenge and the patient’s plasma RAS gene mutation status at the time of rechallenge. This analysis was accomplished via liquid biopsy using OncoBEAMTM RAS CRC Kit to determine the status of RAS gene mutations in circulating tumor DNA of mCRC patients prior to and during anti-EGFR therapy re-challenge. Results showed that the re-challenge of mCRC patients with anti-EGFR monoclonal antibody drugs improved the prognosis (progression-free survival7 and overall survival8) more for RAS wild-type patients than for RAS mutant patients. The results of this research, presented at ASCO (Free ASCO Whitepaper)-GI 2020, indicated the clinical utility of liquid biopsy for RAS gene mutation testing for colorectal cancer when deciding on the re-challenge of anti-EGFR monoclonal antibody drugs.

Since obtaining tumor tissue biopsy samples from metastatic sites place undue physical burden on patients, the liquid biopsy approach to determine RAS mutation status from blood samples is clearly a less invasive approach. Moreover, a liquid biopsy RAS mutation test gives the most timely RAS mutation result at the time of recurrence and anti-EGFR re-challenge, rather than relying on data obtained from testing archival tumor tissue samples. Going forward, progress on prospective6 studies to verify the effectiveness of decisions to re-challenge mCRC patients with anti-EGFR monoclonal antibody drugs informed by OncoBEAMTM RAS CRC Kit for RAS gene mutation testing is expected to contribute to the clinical implementation and utility of this test in the re-challenge treatment of anti-EGFR monoclonal antibody drugs.

By delivering new methods for diagnosing cancer to patients as quickly as possible, Sysmex is taking the lead in the global realization of personalized medicine and contributing to the enhancement of patients’ quality of life and advances in healthcare.

Data Sheet

Presented at: American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium 2020 (ASCO-GI 2020)
Date: January 23–25, 2020
Poster number: 166
Title: RAS status in circulating-tumor DNA (ctDNA) and outcomes during rechallenge treatments with anti-EGFR antibodies in metastatic colorectal cancer (mCRC)

The study was performed on the association between the presence of RAS gene mutations (RAS wild-type patients (10 cases) and RAS mutant patients (6 cases)) and clinical outcome for patients receiving rechallenge with Cetuximab or Panitumumab (16 cases). Prior to re-challenge of antiEGFR monoclonal antibody drugs, OncoBEAMTM RAS CRC Kit was used to measure RAS gene mutations in plasma samples.

The results showed significantly longer survival for RAS wild-type patients than for RAS mutant patients, both for progression-free survival (4.7 months for RAS wild-type patients and 2.3 months for RAS mutant patients) and overall survival (16.0 months for RAS wild-type patients and 3.8 months for RAS mutant patients). These results point to the clinical utility of RAS gene testing using liquid biopsy prior to re-challenge of anti-EGFR monoclonal antibody drugs and are expected to contribute to the determination of more appropriate treatment methods.

Terminology

1 RAS gene: As the likelihood is high that patients with RAS gene (KRAS/NRAS gene) mutations will not benefit (prolongation of life, tumor reduction) from the administration of anti-EGFR drugs, companion diagnostics may be performed to treat the gene mutation first.

2 Liquid biopsy: Similar in performance to a biopsy, which is carried out on a sample taken from tissue such as tumors, but which attempts to reduce the burden on the patient by using blood tests.

3 BEAMing technology: This gene analysis method combines ultrahigh-sensitivity PCR and flow cytometry technologies. BEAMing technology is used to capture individual DNA molecules with magnetic particles in droplets measuring several microns in diameter and then detecting the amplification of the DNA molecules on the magnetic particles. OncoBEAM RAS CRC Kit based on BEAMing technology is an in vitro diagnostic test (in vitro diagnostic medical device registration number: 30100EZX00010000, MHLW-approved on July 19, 2019, Manufactured and supplied by Sysmex) for detecting RAS mutations in ctDNA extracted from the plasma of colorectal cancer patients.

4 JACCRO CC-08AR test: Biomarker research related to a Phase II clinical trial on the re-challenge of Cetuximab for tertiary treatment of KRAS gene wild-type unresectable, advanced, recurrent colorectal cancer to patients with a history of treatment with the anti-EGFR monoclonal antibody drug Cetuximab

5 JACCRO CC-09AR test: Biomarker research related to a Phase II clinical trial on the re-challenge of Panitumumab for tertiary treatment of KRAS gene wild-type unresectable, advanced, recurrent colorectal cancer to patients with a history of treatment with the anti-EGFR monoclonal antibody drug Panitumumab

6 Prospective/retrospective: A prospective (forward-looking) study refers to an epidemiological survey method indicating that information is to be gathered from the start of the survey forward into the future. By contrast, retrospective (backward-looking) studies indicate the gathering of patient information retroactive from the start of the study.

7 Progression-free survival: The period during treatment (following treatment) when cancer is not progressing and the condition is stable.

8 Overall survival: The period of a patient’s survival, beginning with the registration date of a clinical study

On March 4, 2020 DeMelle OncoPharma LLC ("DeMelle" or the "Company"), a clinical-stage biotechnology company, reported an exclusive global licensing agreement with Moffitt Cancer Center to develop DM3001, a first-in-class targeted pancreatic cancer treatment (Press release, DeMelle OncoPharma, MAR 4, 2020, View Source [SID1234556989]). Under the terms of the agreement, DeMelle will utilize Moffitt’s technology as a platform for developing innovative treatments against cancers expressing the novel Exportin-2 target. Based on the underlying biology, lead-product candidate DM3001 (Farnesyl-Di-Methyl-Chromanol) is also expected to treat and prevent a broad range of other cancers, currently under exploration.

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"DeMelle plans to continue building on the significant scientific advancements achieved by Mokenge Malafa, M.D., and his colleagues at Moffitt, with the potential to bring novel treatments that modulates the novel Exportin-2 target," said George Bobotas, Ph.D., CEO of DeMelle OncoPharma.

In a Phase 1b clinical study of 25 pre-surgical pancreatic cancer patients, DM3001 demonstrated promising activity with minimal adverse events. In this study, DM3001 penetrated the pancreatic stromal barrier to produce regulated cell death in tumor cells with a minimal effect on normal tissue. In animal studies, DM3001 inhibited pancreatic and colon cancer growth and metastasis through suppression of cancer stem cells by the NF-κB, STAT3, WNT and RAS/KRAS/MAPK/AKT pathways. DM3001 also demonstrated superior activity compared to standard of care, Gemcitabine.

"With this agreement, DeMelle can build on the research done at Moffitt, and bring novel treatments to patients that have the potential to be safer and more effective," said Dr. Malafa, a surgical oncologist in the Department of Gastrointestinal Oncology at Moffitt. "Because new approaches to treating pancreatic cancer are badly needed, we are pleased to work with DeMelle to give patients more therapeutic options."

Haskell Adler, Ph.D., MBA, senior licensing manager in Moffitt’s Office of Innovation and Industry Alliances added, "I am impressed with the track record of the DeMelle team and look forward to their progress in bringing new therapeutics to market."