On November 22, 2019 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported presentation of the full results from the Toca 5 Phase 3 trial evaluating Toca 511 & Toca FC in patients with recurrent high grade glioma (HGG) at the Society for Neuro-Oncology (SNO) Annual Meeting (Press release, Tocagen, NOV 22, 2019, View Source [SID1234551625]). The data were presented on behalf of the Toca 5 clinical investigators by Timothy Cloughesy, M.D., professor of neurology and director of the neuro-oncology program at the University of California, Los Angeles and principal investigator for the Toca 5 trial.

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Trial design and demographics
Toca 5 was a Phase 3 randomized trial of Toca 511 & Toca FC in patients with recurrent HGG, undergoing resection. The trial involved 67 sites globally and enrolled 403 patients. Patients were randomized 1:1 prior to surgical resection to receive either the Toca 511 & Toca FC regimen or standard of care (SOC) treatment (lomustine, temozolomide or bevacizumab). The primary endpoint of the trial was overall survival (OS) and secondary endpoints included durable response rate, durable clinical benefit rate, duration of durable response and overall survival at 12 months. Patients were stratified based on IDH1 mutation status, KPS and geographic region. The baseline demographics and disease characteristics of the study were well balanced in the intent to treat populations and the 26 pre-specified subgroups.

Results
As previously announced, the trial did not meet the primary or secondary endpoints. The safety, tolerability and adverse event profile of Toca 511 & Toca FC was as expected for this patient population. In the ITT population, the median number of cycles of Toca FC was two and the median number of cycles across the SOC options ranged from two to four.

In a pre-planned subgroup analysis, subjects with second recurrence (N=60) showed a 57% risk reduction for death when treated with Toca 511 and Toca FC (21.82 months median OS compared to 11.14 months, HR=0.43, p=0.0162) representing an approximate doubling of survival. Further analysis of the second recurrence subgroup showed that patients with IDH1 mutations and anaplastic astrocytoma (AA), had the greatest survival benefit (HR=0.102, p=0.009). Second recurrence patients with IDH1 mutations and AA received a median of six cycles of Toca FC compared to a median of three cycles across the SOC options.

"The positive outcome for patients at second recurrence in the Toca 5 trial are compelling, despite the disappointment of the overall trial results," said Dr. Cloughesy. "Combined with an acceptable safety profile, these data support a potential opportunity to address the high unmet needs of this well-defined patient population and should inform any future development of the Toca 511 & Toca FC regimen."

In addition, molecular data from the Toca 5 trial were presented by Michael A. Vogelbaum, M.D., Ph.D., program leader of neuro-oncology and chief of neurosurgery at the Moffitt Cancer Center, at the Society for Neuro-Oncology and Society for CNS Interstitial Delivery of Therapeutics’ 3rd Joint Conference on Therapeutic Delivery to the CNS. Data indicated that the immunological profile at baseline was well balanced between the two arms of the trial. In addition, data showed that patients in the second recurrence, IDH1 mutations and AA subgroups had a more robust immune profile prior to treatment. These data suggest that patients within these subgroups may have been favorably predisposed to generate anti-tumor immune responses.

"We have conducted a thorough analysis of the Toca 5 data and a subgroup of patients appear to benefit from treatment with Toca 511 & Toca FC," said Marty Duvall, chief executive officer of Tocagen. "We have submitted the data to FDA and anticipate providing an update once we have more clarity on potential next steps for our recurrent brain cancer program."

Copies of Dr. Cloughesy’s and Dr. Vogelbaum’s presentations are available on Tocagen’s website.

On November 22, 2019,Generex Biotechnology Corporation ("Generex") reported that it has entered into a definitive Stock Purchase Agreement (the "SPA") for the purchase of 51% of the outstanding capital stock (the "ALTuCELL Stock") of GH Care, Inc. DBA ALTuCELL, Inc.("ALTuCELL"). The ALTuCELL Stock consists of newly issued shares of ALTuCELL (Filing, 8-K, Generex, NOV 22, 2019, View Source [SID1234554201]).

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ALTuCELL has a broad patent portfolio for cell encapsulation technology and cellular therapy The ALTuCELL patent portfolio includes global patents for the AltuCapsÒ cell encapsulation platform, together with patents for the chemistry, manufacturing, and ultra-purification of capsules. ALTuCELL has also been granted a wide-ranging patent, Microencapsulation of Myofibroblasts (Stem cells) Isolated from Wharton Jelly for Prevention and Treatment of Autoimmune and Inflammatory Diseases.

Gary Harlem is ALTuCELL’s President & Chief Executive Officer.

Under the SPA, in exchange for the ALTuCELL Stock, Generex will

•Issue to ALTuCELL 1,600,000 shares of Generex common stock with an initial attributed value of $2.50 per share. If the market price per share of the Generex common stock is below $2.50 on the 6-month anniversary of the closing date, the attributed price of the Generex shares will be repriced to market with a floor of $1.25 per share, and Generex will deliver the number of GNBT shares required to make up the difference in total value.
•Pay $2.5 million in cash ($112,000 of which has already been paid).
In addition to stock and cash at closing, Generex has agreed to pay up to an aggregate of $3,500,000 to ALTuCell upon ALTuCell’s attainment of certain milestones, as follows:

$500,000 upon initiating a first-in-human clinical trial of Altsulin, microencapsulated Sertoli Cells.
$2,000,000 upon initiating a human clinical trial of a cell therapy product using ALTuCAPS microencapsulation technology in the United States.
$1,000,000 upon completing a business development deal with a biopharmaceutical company partner.

The milestone payment shall be made in cash or Generex stock at ALTuCELL’s option. Generex stock will have an attributed value of the lower or $2.50 per share or the market price at time of milestone attainment, but no lower than $1.25

If Generex fails to make a milestone payment within 60 days of ALTuCELL achieving a milestone, Generex will be required to return ALTuCELL Stock commensurate with the failed milestone payment.

Closing of the transaction, anticipated to occur before the end of December, 2019, is subject to customary conditions, including each party’s satisfaction with its due diligence and board of directors’ approval.

Following closing, for so long as Generex owns not less than fifty-one percent (51%) of the issued and outstanding equity securities of ALTuCELL, the size of ALTuCELL’s Board of Directors shall be set at five (5) composed of (i) the CEO of ALTuCELL, (ii) one officer of ALTuCELL, (iii) the CEO of Generex, (iv) one appointee of the Generex, and (v) one independent director, mutually agreed upon by Generex and ALTuCELL.

ALTuCELL is required to deliver certain audited financial statements at Closing. In the event that the financial statements are not delivered Generex is entitled, in its sole discretion, to rescind the transaction.

On November 22, 2019 Dr. Reddy’s Laboratories Ltd. (BSE: 500124, NSE: DRREDDY, NYSE: RDY, along with its subsidiaries together referred to as "Dr. Reddy’s") reported the launch of Doxercalciferol Injection, 4 mcg/2 mL (2 mcg/mL) Multiple-Dose Vials, the therapeutic generic equivalent of Hectorol (doxercalciferol) Injection 4 mcg/2 mL (2 mcg/mL) Multiple-Dose Vials, approved by the U.S. Food and Drug Administration (USFDA) (Press release, Dr Reddy’s, NOV 22, 2019, View Source [SID1234551610]).

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The Hectorol Injection 4 mcg/2 mL (2 mcg/mL) Single-Dose Vials and Multiple-Dose Vials brand and generics had U.S. sales of approximately $138 million MAT for the most recent twelve months ending in September 2019 according to IQVIA Health*.

Hectorol is a trademark of Sanofi-Aventis US LLC.

*IQIA Retail and Non-Retail MAT September 2019

RDY-0919-266

On November 22, 2019 Medical Marijuana, Inc. ("the Company") (OTC: MJNA), the first-ever publicly traded cannabis company in the United States that launched the world’s first-ever cannabis-derived nutraceutical products, brands and supply chain, reported its financial results for the quarter ended September 30, 2019, and provided an overview of recent operational highlights (Press release, Medical Marijuana Sciences, NOV 22, 2019, View Source [SID1234551626]).

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Third Quarter 2019 Financial and Operating Highlights

Generated $17.7 million in revenue for the third quarter of 2019;
Year to date revenue of $58.6 million, a 30% increase over the same period in 2018;
Generated $271,567 of cash from operations in the quarter ended September 30, 2019, with total cash balance of $5.5 million at quarter-end;
Year to date gross profit of $44.5 million, nearly a 44% increase over the same period in 2018;
Cost of Goods Sold for the first nine months decreased as a percentage of sales from 31.4% in 2018 to 24.1% in 2019;
Subsidiary Kannaway became a member of the European Industrial Hemp Association;
Subsidiary HempMeds launched its new CBD pet product line, Hemp for Pets;
The Company and its subsidiary Kannaway were honored with two Stevie Award International Business Awards;
The Company reached a one-year milestone in its high-level CBD hemp oil stability study;
Subsidiary Kannaway entered a partnership with Endocanna Health to create and sell endocannabinoid DNA testing products;
The Company was listed as a Top 5 Company in the Hemp-Based CBD Market by equity research firm Avise Analytics, Ltd.;
Subsidiary HempMeds Brasil signed an agreement with major online marketplace Dr. Cannabis.
"Medical Marijuana, Inc. and its subsidiaries are excited to continue operating as one of the hemp-based CBD industry pioneers. We are very confident in the continued growth of the global CBD market and encouraged by regulatory developments including the White House’s approval of the U.S. Department of Agriculture’s federal hemp production rules," said Medical Marijuana, Inc. CEO Dr. Stuart Titus. "In the future, we intend to continue scaling our operations to meet the high demands for products across the globe."

Operating Results – Q3 2019 Compared to Q3 2018

Sales for the third quarter of 2019 exceeded $17.7 million, a decrease of 3% over Q3 2018. The Company executed on a strategic profitability plan that resulted in gross margins increasing from 73.8% in Q3 of 2018 to 75.2% in Q3 of 2019.

On November 22, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present positive results from the Phase III IMbrave150 study evaluating Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) (Press release, Hoffmann-La Roche, NOV 22, 2019, View Source [SID1234551611]). The data show statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS), compared with sorafenib, in people with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

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Tecentriq in combination with Avastin reduced the risk of death (OS) by 42% (hazard ratio [HR]=0.58; 95% CI: 0.42–0.79; p=0.0006) and reduced the risk of disease worsening or death (PFS) by 41% (HR=0.59; 95% CI: 0.47–0.76; p<0.0001), compared with sorafenib. Safety for Tecentriq and Avastin was consistent with the known safety profiles of the individual medicines.

"For the first time in a decade, we are seeing a treatment that has improved overall survival for people with unresectable hepatocellular carcinoma compared with the current standard of care," said Levi Garraway, M.D., Ph.D, Chief Medical Officer and Head of Global Product Development. "Tecentriq in combination with Avastin could transform the treatment of this aggressive disease, and we are working closely with global health authorities in the hope of bringing this treatment option to patients as soon as possible."

Over 750,000 people worldwide are diagnosed with HCC, the most common form of liver cancer, every year – with the majority of cases in Asia and almost half of all cases in China. Elsewhere, incidence of liver cancer is on the rise across Europe and the US, with the number of liver cancer cases in the US more than tripling since 1980.

These data will be presented in the Presidential session at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia Congress 2019 on 23 November at 11:00 a.m. (Singapore Standard time) (Abstract LBA3).

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies, across several types of lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMbrave150 study
IMbrave150 is a global Phase III, multicentre, open-label study of 501 people with unresectable HCC who have not received prior systemic therapy. People were randomised 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq was administered intravenously (IV), 1200 mg on day 1 of each 21-day cycle, and Avastin was administered IV, 15 mg/kg on day 1 of each 21-day cycle. Sorafenib was administered by mouth, 400 mg twice per day, on days 1–21 of each 21-day cycle. People received the combination or the control arm treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints were OS and PFS by independent review facility (IRF) per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Additional study endpoints included overall response rate (ORR), time to progression (TTP) and duration of response (DoR), as measured by RECIST v1.1 (investigator-assessed [INV] and IRF) and HCC mRECIST (IRF), as well as patient-reported outcomes (including time to deterioration of patient-reported quality of life), safety and pharmacokinetics.

Key efficacy endpoint results for OS and PFS (co-primary endpoints) are below:

NE, not estimable (Median OS for Tecentriq + Avastin not yet reached. For the control arm, the upper CI limit was not estimable); median follow-up 8.6 months; PFS measured as per IRF RECIST v1.1.

Grade 3-4 adverse events (AEs) occurred in 57% of people receiving Tecentriq and Avastin and 55% of people receiving sorafenib. Grade 5 AEs occurred in 5% and 6% of people, respectively.

About hepatocellular carcinoma
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide.1 Over 750,000 people worldwide are diagnosed with HCC every year,1,2 with the majority of cases in Asia and almost half of all cases in China.2,3 In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest rising cause of cancer-related death, while in Europe liver cancer is also on the rise.4,5,6 HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage.1 The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.7

About the Tecentriq and Avastin combination
There is a strong scientific rationale to support the use of Tecentriq plus Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive metastatic triple-negative breast cancer.

About Avastin
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasise).

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

By applying our seminal research in immune tumour profiling within the framework of the Roche-devised cancer immunity cycle, we are accelerating and expanding the transformative benefits with Tecentriq to a greater number of people living with cancer. Our cancer immunotherapy development programme takes a comprehensive approach in pursuing the goal of restoring cancer immunity to improve outcomes for patients.

To learn more about the Roche approach to cancer immunotherapy please follow this link: View Source