On March 13, 2020 RefleXion Medical, a therapeutic oncology company pioneering the use of biology-guided radiotherapy (BgRT)* to treat all stages of cancer reported it has received marketing clearance from the U.S. Food & Drug Administration (FDA) for stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS) and intensity modulated radiotherapy (IMRT) for its RefleXion X1 machine (Press release, RefleXion Medical, MAR 13, 2020, View Source [SID1234555559]).

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"We are at the forefront of an enormous change in expanding the use of radiotherapy from a treatment solely for early-stage cancer patients to an entirely new group of patients who need it most, those with advanced stage cancer," said Todd Powell, CEO and president of RefleXion. "This initial marketing clearance of our RefleXion X1 machine is a steppingstone on the path to our goal of providing BgRT as a novel treatment modality that will expand the overall radiotherapy market significantly.

"We have been preparing for commercial operations in the brand new factory we opened last year and expect to begin machine shipments within the next quarter," continued Powell.

The RefleXion X1 is the only machine that combines high quality computed tomography (CT) imaging, known as fan-beam CT, with a linear accelerator to reduce motion artifacts that can inhibit accurate targeting of the radiation dose to a patient’s tumor. Its groundbreaking design rotates up to 60 times faster than other linear accelerators and modulates dose delivery from 100 points per beam station. These combined improvements may reduce the side effects of radiotherapy by allowing radiation oncologists to better localize the tumor, reduce patient setup errors and precisely deliver dose to complex tumor targets while avoiding nearby normal structures.

"Transitioning this company from a research effort to what is, as of today, a commercial entity has been a thrilling 10-year journey," said Sam Mazin, Ph.D., founder and CTO of RefleXion. "Along the way, RefleXion has become an organization supported by dedicated and brilliant people in every corner, including our clinical partners. We will celebrate this milestone and then quickly turn our sights to bringing our biology-guided radiotherapy to market."

BgRT, a novel treatment modality under development, uses the biological signature of a tumor to characterize its movement and to deliver a precisely tracked therapeutic radiation dose to the tumor. The RefleXion X1 machine with BgRT is designed to overcome the technical limitations that currently restrict radiotherapy to one or two tumors. Once developed, RefleXion will scale BgRT to treat all visible tumors, even those that move rapidly due to involuntary processes such as breathing or digestion, in the same treatment session.

On March 13, 2020 Portage Biotech Inc. (PBT.U, OTC Markets: PTGEF) ("Portage" or the "Company") is reported that it has filed its third quarter financial statements and accompanying management and discussion (Press release, Portage Biotech, MAR 13, 2020, View Source [SID1234555546]).

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These documents are available on SEDAR and on the Company’s website: www.portagebiotech.com.

Highlights of this quarter include:

• October 2019, Intensity therapeutics announced the dosing of its first patient with a combination of its drug INT230-6 and Merck’s Ketruda. This is part of a clinical trial collaboration agreement with Merck to study this combination

• October 2019, Sentien CEO Brian Miller presented Phase 1b clinical data of SBI-101 in acute renal injury at the 2019 Cell and Gene Meeting

• November 2019, Intensity announced that its experimental product, INT230-6 induced prolonged stable disease with abscopal effects and immune responses in multiple solid tumors. This data was selected for an oral presentation at the 34th annual Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting.

• In the period, further progress on preclinical work and progress made in furthering projects from the other subsidiary’s towards the clinic. The Company also wishes to provide an update on the status of its application (the "Revocation Application") to the Ontario Securities Commission (the "OSC") to revoke an outstanding cease trade order issued on August 2, 2019 (the "CTO").

The Company has resolved almost all comments from the OSC except for one: during the review process, the Company was informed by the OSC that it would be required to file a business acquisition report (BAR) under National Instrument 51-102 Continuous Disclosure Obligations in connection with its acquisition of SalvaRx Limited. Although there is already substantial public disclosure in respect of the acquisition available on SEDAR and the Company’s website, the presentation of financial information in respect of SalvaRx Limited was not in a format in compliance with the BAR requirements. The Company is in the process of compiling the relevant financial records for the creation of a proper BAR and is hopeful it will be able to resolve this issue in the very near future.

As indicated in the Company’s news release of January 30, 2020, the relief being sought under the Revocation Application is discretionary and, as such, no firm estimate can be provided as to-2-

when a revocation order will be issued by the OSC. The Company is confident, however, that a revocation order will be issued and, upon issuance, it is expected that the Company’s common shares will resume trading on CSE almost immediately thereafter.

In the interim, shareholders and investors are reminded that, although trading in the shares of the Company may not currently be effected through CSE, trading is permitted on OTC Markets in the United States as follows:

(a) Under the terms of the CTO, Canadian shareholders may trade the shares of the Company on OTC Markets in the United States provided they use the services of a registered dealer in Canada with access to OTC Markets;

(b) US shareholders may trade through OTC markets using the services of any dealer in the United States; and

(c) Other foreign shareholders, such as those in the United Kingdom, may trade through through the services of any dealer (other than Canadian) with access to OTC Markets.

Each dealer will have their own internal rules regarding the ability of shareholders and investors to trade the Company’s shares on OTC Markets. It is the individual responsibility of each shareholder or investor to satisfy these rules before they may trade.

The common shares of the Company trade on OTC Markets under the symbol "PTGEF".

At the time the revocation order is issued, the Company will announce a date for an annual meeting of shareholders at which the Company will bring shareholders and investors up to date on the current operations of the Company and its future plans. The Company wishes to thank shareholders for their continued patience while the Revocation Application is processed.

On March 13, 2020 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported an update on its clinical pipeline and financial results for the first quarter ended January 31, 2020 (Press release, Advaxis, MAR 13, 2020, View Source [SID1234555547]).

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Key recent corporate and clinical pipeline updates:

●Presented updated clinical data from the ongoing Phase 1/2 ADXS-503 trial at the I/O 360° Conference. Data presented showed that the first two patients treated in the combination arm, who previously progressed on KEYTRUDA, achieved a partial response with substantial tumor shrinkage of nearly 60% and the other patient achieving stable disease with a 25% reduction in a target lesion.
●Presented updated survival data from the Phase 1/2 ADXS-PSA trial at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium. Data highlights include reported median overall survival (95% CI) of 16.4 months (4.0-NR) (n=11) for advanced prostate cancer patients with visceral metastases treated with ADXS-PSA in combination with KEYTRUDA compared to an estimated 11 months with current standard of care. In addition, median overall survival (95% CI) was 33.7 months (15.4-33.7) in all patients treated with ADXS-PSA in combination with KEYTRUDA (n=37).
●Data presented in 2020 suggest that both ADXS-503 and ADXS-PSA may have the potential to enhance or restore sensitivity to checkpoint inhibitors such as KEYTRUDA.
●Announced FDA allowance of its Investigational New Drug Application (IND) for ADXS-504 for the treatment of prostate cancer. ADXS-504 is the Company’s second drug product candidate from its HOT off-the-shelf neoantigen clinical program targeting hotspot mutations and other tumor-associated antigens.
●Closing of a $10.5 million equity financing with two investors.
●Announced a research agreement with Personalis to deploy ImmunoID NeXT Platform in the ADXS-503 clinical program. Personalis will conduct comprehensive tumor immunogenic profiling to enable the identification of predictive composite biomarkers and/or signatures of response, as well as the broad evaluation of potential mechanisms of therapy resistance.

Management Commentary

"We have started our fiscal year with encouraging positive data presented in our ADXS-PSA and ADXS-503 clinical programs," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Importantly, data from both studies suggest that Lm immunotherapies may have the ability to synergistically enhance or restore sensitivity to checkpoint inhibitors which could be a meaningful breakthrough in improving outcomes for advanced and refractory patients. We continue to execute on our HOT off-the-shelf program in NSCLC with enrollment continuing in the combination arm of the study, Part B, and a planned initiation of Part C which will move combination therapy to a first-line setting, later this year. We are also planning to move an additional HOT construct, ADXS-504, for prostate cancer, into the clinic later this year for which the IND was allowed earlier this year."

Mr. Berlin continued, "We are currently evaluating next steps for our ADXS-PSA program based on the promising increases in median overall survival observed in combination with KEYTRUDA. With an anticipated cash runway into mid-2021, we are positioned to explore the early signals of activity in our ongoing trials while advancing additional programs that leverage these important findings."

First Quarter Ended January 31, 2020 Financial Results

During the quarter ended January 31, 2019, the Company recognized $19.4 million in revenue associated with the revenue recognition requirements surrounding the termination of the collaboration agreement with Amgen in 2019; no similar situation existed during the fiscal quarter ended January 31, 2020.

Research and development expenses for the first quarter of fiscal year 2020 were $4.9 million, compared with $6.7 million for the first quarter of fiscal year 2019. The decrease is largely attributable to the winding down of our Phase 3 AIM2CERV and Phase 1 ADXS-NEO studies as announced in June 2019 and October 2019, respectively.

General and administrative expenses for the three months ended January 31, 2020 were approximately $3.0 million compared to $2.7 million in the same three-month period in 2019 as a result of higher business development and legal fees.

As of January 31, 2020, the Company had approximately $34.2 million in cash and cash equivalents. The Company believes this is sufficient capital to fund its obligations, as they become due, in the ordinary course of business until at least mid-2021.

On March 13, 2020 Hutchison China MediTech reported SANET-ep trial (clinicaltrials.gov identifier NCT02588170) demonstrated that surufatinib significantly improves progression-free survival ("PFS") in patients with advanced extrapancreatic (non-pancreatic) neuroendocrine tumors compared to placebo, with a median PFS of 9.2 months versus 3.8 months, respectively (hazard ratio = 0.334, 95% CI 0.223 to 0.499, p<0.0001) (Press release, Hutchison China MediTech, MAR 13, 2020, https://www.chi-med.com/enets-2020/ [SID1234555570]). This presented analysis evaluated the safety profile and adverse events of special interest ("AESI") of surufatinib from SANET-ep data. 93.8% of patients in the surufatinib group and 73.5% of patients in the placebo group had at least one treatment-emergent AESI.

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The analysis concluded that AESIs of Grade 3 or higher hypertension and proteinuria occurred more frequently with surufatinib than with placebo, with the most common (at least 3% of patients) grade 3 or greater AESIs being hypertension (40.3% with surufatinib vs. 16.2% with placebo), proteinuria (23.3% vs. 0) and hemorrhage (3.1% vs. 2.9%). It also concluded that AESIs leading to treatment discontinuation were uncommon, with AESIs leading to dose discontinuation in at least 1% of patients being proteinuria (3.9% with surufatinib vs. 0 with placebo), hemorrhage (1.6% vs 1.5%), and hepatic failure (0.8% vs 1.5%). Surufatinib has a manageable safety profile in patients with advanced extra-pancreatic neuroendocrine tumors.

Title: Safety Profile and Adverse Events of Special Interest for Surufatinib in Chinese Patients with Advanced Extra-Pancreatic Neuroendocrine Tumors: Analysis of the Phase 3 SANET-ep Trial

Authors: Jie Li, Jianming Xu, Zhiwei Zhou, Chunmei Bai, Yihebali Chi, Zhiping Li, Nong Xu, Enxiao Li, Tianshu Liu, Yuxian Bai, Sha Guan, Lin Shen

Abstract: #2914

Introduction The previously reported SANET-ep trial (NCT02588170) demonstrated surufatinib significantly improves progression-free survival (PFS) in patients (pts) with advanced extrapancreatic neuroendocrine tumors (epNETs) compared to placebo; median PFS (9.2 vs. 3.8 months; HR = 0.334, 95% CI 0.223 to 0.499, p<0.0001).

Aims The present analysis evaluates the safety profile and adverse events of special interest (AESIs) of surufatinib from SANET-ep data.

Patients and Methods Pts were randomized (2:1) to receive surufatinib (300 mg once daily continuously) or placebo. Treatment-related AESIs and time-to-first occurrence of AESIs were summarized. Predefined AESIs included hepatic failure (HF), proteinuria (P), hypertension (HTN), haemorrhage (H), and acute renal failure (ARF), which were searched with narrow MedDRA Standardized MedDRA Query (SMQ).

Results A total of 121/129 (93.8%) pts in the surufatinib group and 50/68 (73.5%) in the placebo group had ≥ 1 treatment-emergent AESI; the mean relative dose intensity was 86.42% and 96.78%, respectively. The most commonly reported (>10% of pts) AESIs were P (84.5% vs 57.4%), HTN (68.2% vs 30.9%), and H (55.8% vs 27.9%). The most common (≥3% of pts) grade ≥3 AESIs were HTN (40.3% vs 16.2%), P (23.3% vs 0) and H (3.1% vs 2.9%); the median time-to-onset of these events in the surufatinib group was 13.5, 28, and 32 days, respectively. AESIs (≥1% of pts) leading to dose discontinuation were P (3.9% vs 0), H (1.6% vs 1.5%), and HF (0.8% vs 1.5%).

Conclusions The AESIs of Grade ≥ 3 HTN and P occurred more frequently with surufatinib; however, AESIs leading to treatment discontinuation were uncommon. Surufatinib has a manageable safety profile in pts with advanced epNETs.

Keywords extra-pancreatic, neuroendocrine tumors, safety

On March 13, 2020 Clarity Pharmaceuticals, a radiopharmaceutical company focused on the treatment of serious disease, is reported the signing of a Product Supply Agreement with the Idaho State University Idaho Accelerator Center (IAC) for the production and commercial supply of copper-67 (Cu-67) (Press release, Clarity Pharmaceuticals, MAR 13, 2020, View Source [SID1234555497]).

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Under the new agreement, IAC will supply Clarity with Cu-67 for planned clinical development, including the SARTATETM trial in children with neuroblastoma and SAR-bisPSMA trial in prostate cancer patients in the United States. IAC has been Clarity’s long-term partner, providing a reliable supply of high purity and high specific activity Cu-67 for some years. IAC’s proven experience in the production and supply of Cu-67 has already allowed Clarity to initiate and complete therapeutic studies in a range of cancer types both in the United States and in Australia.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are excited to bolster our relationship with IAC to further progress our pipeline of theranostic agents in the fight against cancer. IAC’s electron accelerator capability enables Clarity to eliminate the reliance on supply from the limited number of aging nuclear reactors which currently produce therapeutic radionuclides such as lutetium-177. This gives Clarity the opportunity to move swiftly through clinical trials with its three main products, SARTATETM, SAR-bisPSMA and SAR-BBN in such indications as neuroblastoma, neuroendocrine tumours, prostate cancer, breast cancer and brain cancers.

"We are pleased to have signed the Product Supply Agreement with Clarity and are looking forward to continuing our supply of this copper isotope using our increased capacity and our world leading e-linac process to produce a high purity product at very high specific activity," said Jon Stoner, director of the IAC. "Clarity’s proprietary chelator technology along with our patent protected commercially produced Cu-67 combine to showcase a future market leading medical isotope."

Dr Taylor further commented, "Clarity is a clinical stage radiopharmaceutical company that is uniquely placed to control its full supply chain within the United States. With IAC further planning on additional facilities to support the development of Cu-67 production and with Clarity having recently signed a Letter of Intent with NorthStar Medical to supply and industrialise the production of this therapeutic isotope, we are well underway towards building stable and reliable commercial-scale supply of Cu-67 for our late-phase trials and market entry of our products in a number of large cancer indications".

About Copper-67 (Cu-67)
Copper-67 (Cu-67) is a short-range, beta-emitting radioisotope which is attractive for medical purposes due to its ability to carry sufficient radiation energy to cause cell death in targeted cells while having a sufficiently short half-life to limit unwanted radioactivity in patients. Cu-67 is being investigated for therapeutic purposes across a wide range of adult and childhood cancers. Potential radiotherapeutic targets include prostate cancer, breast cancer, neuroendocrine tumours (NETs), neuroblastoma, glioma, lymphoma, ovarian cancer and bladder cancers. In order to develop safe and effective targeted therapies, a chelator, which strongly binds Cu-67 to the targeting agent, is required. Clarity Pharmaceuticals has successfully developed a highly specific and highly stable chelator for copper isotopes and is now progressing a range of radiopharmaceuticals based on its proprietary MeCOSar chelator. The IAC has developed a proprietary process for production of high purity and high specific activity Cu-67 to meet demand for clinical research and treatment.