On August 26, 2019 Oncoceutics, Inc. reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for ONC206, allowing the first-in-human trial of the compound (Press release, Oncoceutics, AUG 26, 2019, View Source [SID1234558333]). ONC206 is the first of the family of drug candidates, which we call "imipridones", that possess the same core chemical structure as ONC201.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The first clinical trial for ONC206 in adults with primary central nervous system neoplasms will be conducted at the National Cancer Institute (NCI) under the leadership of Mark Gilbert, MD, Chief of the Neuro-Oncology Branch, Center for Cancer Research (CCR) and Brett Theeler, MD, Clinical Collaborator at the NCI Neuro-Oncology Branch, CCR.

Dr. Gilbert has previously demonstrated that ONC206 exerts therapeutic effects in preclinical models for neuro-oncology indications that are commonly recognized as refractory to standard of care. ONC206 has been studied extensively by several other research groups and showed antitumor activity in different tumor types. Preclinical studies suggest that the properties of ONC206 include penetrance of the blood brain barrier, feasibility of oral administration, demonstration of a well-tolerated safety profile, and selective antagonization of dopamine receptor D2 (DRD2). While DRD2 is targeted by both ONC206 and ONC201, the receptor pharmacology of ONC206 is unique and distinct, which may offer therapeutic options beyond those of ONC201. ONC206 was very well tolerated in GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses that did not reveal any dose-limiting toxicities.

ONC206 is protected by issued composition of matter patents in the USA and Europe.

"We are pleased by the FDA’s acceptance of our IND application for ONC206 that provides further validation of our overall development program," said Martin Stogniew, PhD, Chief Development Officer of Oncoceutics. "The introduction of another imipridone into clinical trials represents a major milestone for the company and demonstrates the therapeutic value of the new class of imipridone compounds.

"DRD2 has emerged as a viable novel target in neuro-oncology and controls diverse signaling pathways. However, druggable ligands to target DRD2 have remained elusive. We are encouraged to see the different biological effects exerted by ONC201 and ONC206 via dopamine receptor activated pathways, including their synergistic cooperation that clearly demonstrates the multi-functionality of this G protein-coupled receptor. The common features of both compounds that include high penetrance of the blood brain barrier, convenient oral administration and excellent tolerability is rewarding for our patients, in particular children," said Sabine Mueller, MD, PhD, Head of Clinical Programs, DIPG Center of Expertise Zurich and Adjunct Associate Professor, University of California, San Francisco.

"We plan to evaluate the safety and clinical activity of ONC206 in patients with central nervous system malignancies," said Dr. Gilbert. "This clinical trial will incorporate biomarker information derived from our molecular studies of ONC206 in an effort to enable future patient selection."

On August 26, 2019 (the "Effective Date"), Alpine Immune Sciences, Inc. (the "Company") and its wholly-owned subsidiary, AIS Operating Co., Inc. ("AIS" and together with the Company, the "Borrowers"), reported that it has entered into an Amended and Restated Loan and Security Agreement (the "Loan Agreement") with Silicon Valley Bank (the "Bank"), pursuant to which the Bank agreed to extend term loans to the Company with an aggregate principal amount of up to $15.0 million (the "Term Loans") (Filing, 8-K, Alpine Immune Sciences, AUG 26, 2019, View Source [SID1234551115]). The Company intends to use the proceeds to replace and refinance AIS’ existing loan facility pursuant to the Loan and Security Agreement by and between AIS and the Bank dated as of December 16, 2016 (the "Original Agreement"), as well as for potential working capital and other general corporate purposes, including the advancement of the Company’s development programs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Borrowings under the Loan Agreement will consist of up to three separate tranches. The initial tranche of $5.0 million was funded on August 26, 2019, $3.0 million of which will be used to repay amounts owing under the Original Agreement. The second tranche of up to $5.0 million is available in multiple advances at the Borrowers’ option at any time through April 30, 2020. The third and final tranche of up to $5.0 million is available in multiple advances at the Borrowers’ option at any time from the date on which Bank receives and approves evidence that the Borrowers have initiated a Phase 2a trial of ALPN-101 in psoriatic arthritis through July 31, 2020. Each term loan advance, other than the final term loan advance, must be in an amount of not less than $0.5 million and, after repayment, no term loan advance may be re-borrowed.

The Term Loans shall accrue interest at a floating per annum rate of 0.25% above the prime rate, subject to a floor of 5.75%, which interest is payable monthly commencing in September 2019. Upon the occurrence and during the continuance of an event of default, a default interest rate will apply that is 4.0% above the otherwise applicable interest rate. The Term Loans are interest only until September 30, 2020, after which the Term Loans will be payable in 34 equal monthly installments of principal plus interest, with the final installment due and payable on July 1, 2023. If Borrowers receive aggregate net new capital of at least $40 million on or prior to June 30, 2020, the Term Loans will be interest-only until June 30, 2021, after which the Term Loans will be payable in 25 equal monthly installments of principal plus interest, with the final installment due and payable on July 1, 2023.
The Borrowers may prepay all, but not less than all, of the Term Loans subject to a prepayment fee equal to $75,000, which represents the deferred portion of the final payment due under the Original Agreement, plus the outstanding principal balance under the Term Loans at the time of such prepayment multiplied by (i) 2.0%, if the prepayment occurs on or prior to the first anniversary of the Effective Date, (ii) 1.0%, if the prepayment occurs after the first anniversary of the Effective Date, but on or prior to the second anniversary of the Effective Date or (iii) 0%, if the prepayment occurs after the second anniversary of the Effective Date, but prior to the maturity date for the Term Loan. A fee in the amount of 5.5% of the Term Loans funded is payable to the Bank on the date on which the Term Loans are prepaid, paid or become due and payable in full.
The Loan Agreement contains customary representations and warranties, events of default (including an event of default upon a material adverse change of the Borrowers) and affirmative and negative covenants, including, among others, covenants that limit or restrict the Borrowers’ ability to, among other things, incur additional indebtedness, grant liens, merge or consolidate, make acquisitions, pay dividends or other distributions or repurchase equity, make investments, dispose of assets, engage in any new line of business, and enter into certain transactions with affiliates, in each case subject to certain exceptions. As security for its obligations under the Loan Agreement, the Borrowers granted the Bank a first priority security interest on substantially all of Borrowers’ assets, except intellectual property, and subject to certain other exceptions.
The foregoing description of the Loan Agreement is not complete and is qualified in its entirety by reference to the full text of the Loan Agreement, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated by reference herein.

On August 26, 2019 Gilead Sciences, Inc. (Nasdaq: GILD) reported that Daniel O’Day, Gilead’s Chairman and Chief Executive Officer, will participate in a fireside chat at the Morgan Stanley Global Healthcare Conference in New York on Tuesday, September 10 at 10:00 a.m. Eastern Time (Press release, Gilead Sciences, AUG 26, 2019, View Source [SID1234539018]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The audio portion of the fireside chat will be accessible live through the company’s Investors page at View Source Please connect to the company’s website at least 15 minutes prior to the start of the presentation to ensure adequate time for any software download that may be required to listen to the webcast. The replay will be available for 14 days following the presentation.

On August 26, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported that the company plans to present at the following conferences in September (Press release, Iovance Biotherapeutics, AUG 26, 2019, View Source [SID1234539017]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

RW Baird 2019 Global Healthcare Conference in New York, Sept. 4-5, 2019
Location: InterContinental New York Barclay
Date/Time: Wednesday, Sept. 4, at 3:45 p.m. EDT
Wells Fargo Securities 2019 Healthcare Conference in Boston, Sept. 4-5, 2019
Location: The Westin Copley Place
Date/Time: Thursday, Sept. 5, at 8:35 a.m. EDT
H.C. Wainwright 21st Annual Global Investment Conference in New York, Sept. 8-10, 2019
Location: Lotte New York Palace
Date/Time: Monday, Sept. 9, at 8:45 a.m. EDT
Live and archived webcasts of the presentations will be available by visiting the Investors section of the Iovance Biotherapeutics website at View Source

On August 26, 2019 Bio-Path Holdings, Inc., (NASDAQ:BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported patient dosing in Bio-Path’s amended Phase 2 trial of prexigebersen for the treatment of acute myeloid leukemia (AML), as announced in March 2019 (Press release, Bio-Path Holdings, AUG 26, 2019, View Source [SID1234539010]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The key change in the amended Phase 2 study is the inclusion of patients with high risk myelodysplastic syndrome (MDS) and refractory/relapsed AML patients. The restructured Phase 2 clinical trial has two cohorts of patients. The first being untreated AML patients as existed in the pre-amended trial but with the addition of high risk MDS patients, and a second cohort comprised of refractory/relapsed AML patients and high risk MDS patients.

The amended Phase 2 study will continue evaluating the safety of prexigebersen in combination with decitabine in both cohorts of patients at a dose of 60 mg/m2 in combination with decitabine. The study will include a total of six evaluable patients for a safety assessment of prexigebersen and decitabine. To date, the Company has enrolled five evaluable patients: three untreated AML patients in who received therapy prior to amending the trial, and two patients who are now being treated under the amended Phase 2 trial. Assuming a successful completion of this safety assessment, the study will then modify testing of both cohorts of patients to add venetoclax to the prexigebersen/decitabine combination treatment.

After a six-patient safety assessment of the prexigebersen/decitabine/venetoclax combination, the Company intends to commence the efficacy segment of this trial. It is anticipated that each cohort will include an interim assessment of 19 evaluable patients that would assess whether the treatment efficacy of the combination of prexigebersen/decitabine/ venetoclax exceeds the efficacy of current standard-of-care therapy with statistical significance. Upon such favorable data, Bio-Path would petition the U.S. Food and Drug Administration (FDA) for accelerated approval. The efficacy segment of the trial is expected to be conducted at up to ten clinical sites in the United States. Moving forward, the Company intends to evaluate potential clinical sites in Europe with an emphasis on patient accruals.

"We are excited to have dosed the first patient in our amended protocol of this important clinical trial, confident that the changes made to the protocol, along with the inclusion of MDS patients, will further demonstrate the potential of prexigebersen in a number of cancer indications for which there are limited treatment options," said Peter Nielsen, President and Chief Executive Officer of Bio-Path. "We are encouraged about the outcome for this study, as preclinical work showed the benefit of prexigebersen in combination with decitabine and venetoclax. We look forward to advancing this development program with the goal of bringing new therapies to cancer patients in need."