On May 6, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has approved Kadcyla (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (eBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin (trastuzumab)-based treatment (Press release, Hoffmann-La Roche, MAY 6, 2019, View Source [SID1234535752]).

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"This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot programme, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "With every step forward in reducing the risk of disease recurrence, we come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure."

The goal in treating eBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach.1,2 While we come closer to this goal with each advance, many people still have a disease recurrence in the long-term.3 Neoadjuvant treatment is given before surgery with the goal of shrinking tumours and helping to improve surgical outcomes.2 Adjuvant treatment is given after surgery and aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning.2

The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes, leading to an approval in just over 12 weeks after completing the submission. Kadcyla is the first Roche medicine approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.4 For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.5

This approval is based on results of the phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin as an adjuvant treatment in people with HER2-positive eBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment.6 At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%.6 People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.7,8

The most common Grade 3 or higher side effects (>2%) with Kadcyla in the KATHERINE study were decreased platelet count and high blood pressure. The most common side effects (>25%) with Kadcyla were fatigue; nausea; increased blood levels of liver enzymes; musculoskeletal pain; bleeding; decreased platelet count; headache; numbness, tingling or pain in the hands or feet; and joint pain.6,9

About the KATHERINE study10
KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomisation free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include iDFS including second primary non-breast cancer, disease-free survival and overall survival.

About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.11,12 It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.13 Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.14 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.

On May 6, 2019 PIN Pharma, a company focused on modulating the immune system and having its first indication in oncology, reported the Company will be presenting a poster at the 55th Annual meeting of ASCO (Free ASCO Whitepaper) in Chicago on June 1 between 8:00 AM – 11:00 reporting the results of the first-in-human trial evaluating the immune activation and safety of PIN-2 administered to patients with advanced solid tumors (Press release, PIN Pharma, MAY 6, 2019, View Source [SID1234535772]).

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About PIN-2

PIN-2 is a novel immunomodulatory peptide with a unique mechanism of action in that it links the innate and adaptive immune systems, resulting in an enhanced immune response. In vitro and in vivo preclinical studies have shown that PIN-2 rapidly and preferentially penetrates monocytes, modifies the mRNAs involved in the induction of innate immune activation (with an attendant link to the adaptive immune system), and promotes endogenous cytotoxic T lymphocytes infiltration at the tumor site. PIN-2 acts upstream of other immune-based treatment modalities.

Given its unique, upstream immunomodulatory activity, its extensive preclinical body of evidence, and its first-in-human study results, PIN-2 holds the potential to be a new strategy in the fight against cancer and cancer-mediated immunosuppression. Further clinical research is warranted to evaluate the full potential of PIN-2 in cancer care.

On May 6, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that John Prendergast, Heat Biologic’s Lead Board member, is scheduled to present at the ChinaBio 2019 conference on Thursday, May 9th, at 2:15 PM China Standard Time (CST), which is being held at Pudong Ballroom 5, 3F, Kerry Hotel in Pudong, Shanghai, China (Press release, Heat Biologics, MAY 6, 2019, View Source [SID1234535753]).

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Additional information on the conference is available at: View Source

On May 6, 2019 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that advances have been completed in the manufacturing process for the clinical trial product that will be used in PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, MAY 6, 2019, View Source [SID1234535773]).

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Since PharmaCyte’s last press release describing the manufacturing process for its clinical trial product and the testing of that product, the data from the manufacturing process has been reviewed, analyzed and discussed in great detail among PharmaCyte’s management team, including the leader of its clinical development program in pancreatic cancer and designated Principal Investigator (PI) for the LAPC trial, Prof. Manuel Hidalgo of the Harvard Medical School, Austrianova’s management team (the manufacturer of the clinical trial product), cGMP Validation (PharmaCyte’s cGMP expert consulting firm), Eurofins Lancaster Laboratories (who produced the cells for PharmaCyte’s Master Cell Bank) and several consulting cellular biologists.

The data obtained to date from the encapsulation parameters of the manufacturing process itself indicate that the encapsulation portion of the process is fault free and reproducible, which is a fundamental requirement of the FDA.

On the advice of PharmaCyte’s cGMP expert, the company plans to conduct two additional and staggered manufacturing runs in order to maximize the chances for a successful IND submission given the novelty and complexity of the entire process. In the time since the last manufacturing run, which we reported on in January of this year, those involved with the manufacturing process have been concentrating on changes that can be made to improve the process. We believe that these changes will improve the cGMP manufacturing process to the point that the entire process can be shown to be consistently reproducible and robust as required by the FDA, and to ensure that the end-products of these manufacturing runs will convert the cancer prodrug ifosfamide into its cancer-killing form as well as they should.

This intensive effort has involved several independent tests by Austrianova and Eurofins. The results of these tests strongly indicate that, after the suggested changes are implemented, positive results should be obtained. When the changes are made to the cGMP manufacturing process, they should significantly improve the growth of the cells obtained from the Master Cell Bank both before and after encapsulation takes place. PharmaCyte and Austrianova and its team of consultants are in the final stages of optimizing this aspect of the manufacturing process.

Meanwhile, PharmaCyte’s clinical development program in pancreatic cancer is progressing. As explained by Prof. Hidalgo, "PharmaCyte has a strong clinical trial program for pancreatic cancer. The trial design has been thoroughly vetted by a team of the best pancreatic cancer specialists in the country. I continue to lead PharmaCyte’s program in pancreatic cancer, and I am eager to get underway as its PI for the LAPC trial. Members of PharmaCyte’s team are working on various aspects of implementing the program. I remain excited about the potential that PharmaCyte’s technology can offer patients who are suffering from LAPC and am looking forward to what a successful trial may mean for the way some types of solid cancerous tumors are treated in the future."

On May 6, 2019 Arbutus Biopharma Corporation (Nasdaq: ABUS), an industry-leading Hepatitis B Virus (HBV) therapeutic solutions company, reported its first quarter 2019 financial results and provides a corporate update (Press release, Arbutus Biopharma, MAY 6, 2019, View Source [SID1234535794]).

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"Arbutus is committed to the development of an effective combination regimen to achieve an HBV cure. We continue to believe that the development of a cure for chronic HBV can best be achieved by employing a combination of therapeutic agents with complementary mechanisms of action," said Dr. Mark J. Murray, President and Chief Executive Officer of Arbutus. "Our pipeline, of proprietary therapeutic agents that target HBV replication and HBsAg expression could in combination, lead to a cure. "

Recent Clinical Accomplishments and Key Corporate Objectives
AB-506

In a Phase 1a/1b clinical trial, AB-506, Arbutus’ oral capsid inhibitor, successfully progressed through the healthy volunteer portion and is currently being administered in two dose levels to HBV patients in the 28-day multiple dose portion of the trial. Top-line results of an interim analysis from this Phase 1a/1b clinical trial are expected in July 2019 at which time we expect to disclose information on clinical safety in healthy volunteers and safety and efficacy data in chronically infected HBV patients at both dose levels. We intend to present more detailed information on the trial at an upcoming scientific conference towards the end of 2019.

A Phase 2a dose-finding and long-term safety trial of AB-506 with an approved nucleoside analogue is planned to initiate late in the second half of the year to support the use of AB-506 in future combination registration trials.
AB-729

AB-729, an RNAi agent which blocks HBsAg expression that is administered subcutaneously and is intended to be dosed monthly, has successfully completed IND-enabling studies in support of the single ascending dosing portion of a Phase 1a/1b clinical trial which the Company filed as part of a Clinical Trial Application. On May 3rd, a regulatory authority requested that the Company complete its ongoing 3- and 6-month toxicology studies before commencing the single ascending portion of the Phase 1a/1b clinical trial, which was planned for this quarter. As a result of this request, the clinical trial start will be delayed. We will explore options to accelerate its initiation based on the currently available toxicology study duration and update the market when the clinical trial start date is fixed.
RNA Destabilizer Program

Arbutus remains committed to the development of oral RNA-destabilizers that have shown compelling anti-viral effects in multiple HBV preclinical models. AB-452, Arbutus’ lead oral RNA-destabilizer is being evaluated in a series of in vitro and in vivo studies to further characterize the compound, its mechanism of action, safety and pharmacokinetic profile before deciding whether to initiate clinical trials. Following careful assessment of the nonclinical safety findings that led to pausing the entry of AB-452 into human clinical studies, we have concluded that the nonclinical safety study resulted in several confounding observations which included clinical observations with no histological correlation, a lack of dose response regarding some key findings and an unexplained vehicle effect. Because of these confounding observations, we have determined that repeating the 90-day preclinical safety study in two species is appropriate before making a go/no-go decision. We expect that the results of this study will allow us to make that decision early in 2020.

In parallel, the Company is advancing several follow-on compounds, with distinct chemical scaffolds, into the lead optimization stage, with a goal of having a 2nd generation candidate nominated for development by the end of 2019.
Dr. Michael J. Sofia, Arbutus’ Chief Scientific Officer, stated, "We continue to believe that oral RNA destabilizers represent a very relevant and important therapeutic approach to treating HBV. We also believe we continue to have the most advanced program of this kind in the HBV field and that success here could be very significant for HBV patients, as well as for Arbutus."

Early R&D Programs

The Company continues a robust discovery effort focused on follow on compounds for its current pipeline, including further advancements in the Company’s capsid inhibitors and RNA destabilizers as well as discovery efforts focused on reawakening HBV patients’ immune response and novel HBV-specific targets such as compounds targeting PD-L1 and HBV cccDNA.
ONPATTRO Royalty Entitlement

ONPATTRO is an RNAi therapeutic that has been developed for the treatment of hereditary ATTR (hATTR) amyloidosis, and has been approved by the FDA and the EMA. Arbutus has a royalty entitlement on global sales of ONPATTRO for the LNP technology licensed by Arbutus to Alnylam for this product. The Company began recognizing royalty income in 2018. The royalty rate is tiered, based on product sales, and in the low to mid-single digits.

Financial Results

Cash, Cash Equivalents and Investments

Arbutus had cash, cash equivalents and short-term investments totaling $110.6 million as of March 31, 2019, as compared to $124.6 million as of December 31, 2018. The $14.0 million decrease for the three months ended March 31, 2019 was due primarily to $16.5 million of cash used in operating activities partially offset by $2.6 million of proceeds from the issuance of shares under its ATM program. We believe our cash and investments balance is sufficient to fund operations into 2020.

Operating Expenses

Research and development expenses for the three months ended March 31, 2019 were $14.8 million compared to $13.9 million for the three months ended March 31, 2018. Research and development expenses for the three months ended March 31, 2019 included costs associated with the Company’s Phase 1a/1b clinical trial for its lead capsid inhibitor (AB-506), pre-clinical studies for its RNAi agent (AB-729), and characterization activities for its HBV RNA Destabilizer (AB-452). General and Administrative expenses for the three months ended March 31, 2019 were $4.4 million compared to $3.7 million for the three months ended March 31, 2018.

Equity investment loss

The Company recorded a loss of $4.7 million in the first quarter of 2019 for its proportionate share of Genevant’s net loss, a company launched with Roivant Sciences Ltd. There was no comparable amount for the first quarter of 2018. Financial results of Genevant are recorded on a one-quarter lag basis. The Company currently owns approximately 40% of the common equity of Genevant as of March 31, 2019.

Net Loss

For the three months ended March 31, 2019, net loss attributable to common shares was $26.0 million ($0.47 basic and diluted loss per common share) as compared to $19.8 million ($0.36 basic and diluted loss per common share) for the three months ended March 31, 2018. Net loss attributable to common shares for the three months ended March 31, 2019 included $2.7 million of non-cash expense for the accrual of coupon on its convertible preferred shares. The increase in net loss is due primarily to the equity investment loss in Genevant.

Outstanding Shares

The Company had approximately 55.7 million common shares issued and outstanding as of March 31, 2019. In addition, the Company had approximately 7.7 million 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. Assuming the outstanding options and convertible preferred shares were fully converted, the Company would have had approximately 86 million common shares outstanding as of March 31, 2019.

Conference Call Today

Arbutus will hold a conference call and webcast today, Monday, May 6, 2019 at 4:30 PM Eastern Time (1:30 PM Pacific 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 9448718.

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 9448718.