On April 27 , 2020 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 the presentation of a poster highlighting the clinical trial design of its Phase 1 study of BP1002 at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held virtually from April 27-28, 2020 (Press release, Bio-Path Holdings, APR 27, 2020, View Source [SID1234556624]).

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The poster, titled, "A Phase I Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1002 (L-Bcl-2) Antisense Oligonucleotide in Patients with Advanced Lymphoid Malignancies," was presented virtually by Dr. Ana Tari Ashizawa, Senior Vice President of Research, Development and Clinical Design at Bio-Path Holdings.

"We are particularly pleased to have our Phase 1 clinical development program for BP1002 as a potential therapy for lymphoma and chronic lymphocytic leukemia patients highlighted in a poster at this important scientific meeting," stated Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "We believe this poster will enhance visibility for our Bcl-2 program among an audience of world-leading oncologists and cancer researchers."

The Phase 1 clinical trial is expected to be conducted at several leading cancer centers, including The University of Texas MD Anderson Cancer Center, the Georgia Cancer Center and the Sarah Canon Research Institute. Initially, a total of six evaluable patients will be treated with BP1002 monotherapy in a standard 3+3 design, with a starting dose of 20 mg/m2. The approved treatment cycle is two doses per week over four weeks, resulting in eight doses administered over 28 days. The primary objective of the study is to evaluate the safety and tolerability of escalating doses of BP1002.

BP1002 targets the protein Bcl-2, which is responsible for driving cell survival in up to 60% of all cancers. High expression of Bcl-2 has been correlated with adverse prognosis for patients diagnosed with relapsed, aggressive non-Hodgkin’s lymphoma. Preclinical studies have shown BP1002 to be a potent inhibitor against the Bcl-2 target, and Bio-Path believes that its benign safety profile should enable BP1002 combination therapy with approved agents.

On April 27, 2020 Aptose Biosciences Inc. (Nasdaq: APTO; TSX: APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported the early clinical data on CG-806, the company’s oral, first-in-class FLT3/BTK cluster selective kinase inhibitor, at the AACR (Free AACR Whitepaper) Virtual Annual Meeting I (April 27-28), in lieu of the live oral presentation originally planned (Press release, Aptose Biosciences, APR 27, 2020, View Source [SID1234556623]).

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Rafael Bejar M.D., Ph.D., Aptose’s Chief Medical Officer, presented a video summary of Abstract # 9967 – Early clinical findings from a phase 1a/b dose escalation trial to evaluate the safety and tolerability of CG-806 in patients with relapsed or refractory CLL/SLL or non-Hodgkin’s lymphomas [link].

The first-in-human tests of CG-806 are being carried out in a Phase 1a/b clinical study. The target population in the study includes patients with significant unmet needs including patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL) or non-Hodgkin lymphoma (NHL) who have failed or been intolerant to two lines of established therapy. CG-806 is administered as oral capsules dosed twice daily in 28-day cycles. The study design includes an accelerated titration followed by a 3+3 dose escalation to establish the recommended Phase 2 dose for planned expansion cohorts and future studies.

The first patient, treated with 150 mg BID of CG-806, was heavily pretreated, carried a TP53 mutation, and had severe thrombocytopenia prior to study entry. This patient currently is in the eleventh cycle of therapy without having experienced a dose-limiting toxicity (DLT) and has been dose escalated to the 450 mg BID dose level.

The second patient, treated at the 300 mg BID dose level, had significant marrow involvement with neutropenia and thrombocytopenia at study entry, and developed a brisk lymphocytosis, but did not experience a DLT through four cycles of therapy including no worsening of their thrombocytopenia or neutropenia.

The study has now completed three dose levels without observing any drug-related severe adverse events (SAE) and has not reached a dose-limiting toxicity. Three patients completed the safety evaluation period at the third dose level, 450 mg BID, and as a result, the fourth dose level was opened. The first patient, previously dosed at 150 mg BID was dose escalated to dose level 3 at 450 mg BID. Enrollment is open and dosing is ongoing at the 600 mg BID dose level with no drug-related SAEs or DLTs encountered to date.

Key findings to date:

No drug-related SAEs or DLTs have been observed in patients to date
CG-806 demonstrates favorable steady state pharmacokinetics evidenced by stable trough plasma concentrations reached by Day 8 in the first two patients treated at dose levels 1 and 2
CG-806 has shown on-target pharmacologic activity demonstrated by plasma inhibitory assays with reporter cells exposed to patient plasma for 6 hours
Phospho-BTK is markedly reduced after exposure to plasma from the patient treated at dose level 1 and completely abrogated with plasma form the patient treated at dose level 2
Similar results are seen for the phosphorylation of PDGFR-alpha, a target of CG-806, for SYK, which lies in the same signaling pathway as BTK and for ERK
Lymphocytosis was noted at dose level 2 – pharmacologic BTK inhibition in CLL promotes exfiltration
Dr. Bejar summarized the team’s findings: "CG-806 is a novel and unique cluster selective kinase inhibitor with activity against clinically validated targets in both lymphoid and myeloid malignancies through its potent inhibition of BTK and FLT3. The ongoing Phase 1 study in relapsed/refractory B-cell malignancies has demonstrated the safety of CG-806 to date, pharmacologic activity, and predictable pharmacokinetic behavior. We look forward to presenting new data from higher dose cohorts at a future medical meeting."

The slide deck of this presentation is available on the Aptose website View Source

About CG-806

CG-806 is an oral, first-in-class FLT3/BTK cluster selective kinase inhibitor and is in Phase 1 clinical studies for the treatment of hematologic malignancies. This small molecule, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of AML in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML and other myeloid malignancies. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent or other non-covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.

On April 27, 2020 Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune/inflammatory diseases, reported the design of NEON-1, the first-in-human study of ALPN-202, a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor, at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I, in the Phase I Trials in Progress Virtual Poster Session (Press release, Alpine Immune Sciences, APR 27, 2020, View Source [SID1234556622]).

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Many patients treated with checkpoint inhibitors fail to achieve an objective or complete anti-tumor response. This could be due to a lack of sufficient T cell costimluation in the tumor microenvironment, such as inadequate CD28 ligands. To address this, ALPN-202 was designed to inhibit both the PD-L1 and CTLA-4 checkpoints, while also providing a CD28 costimulatory signal. Importantly, ALPN-202’s costimulatory function is designed to depend upon PD-L1, to help ensure clinical safety and tolerability.

NEON-1 includes two parts: dose escalation and expansion cohort(s). It will enroll adults with advanced solid tumors or lymphoma refractory or resistant to standard therapy, including checkpoint inhibitors when indicated. Measurable disease is required for most participants, as are an ECOG status of 0 to 2 and adequate hematological, renal, and hepatic function. Dose escalation begins with single-participant cohorts to minimize the number of participants anticipated to receive subtherapeutic doses, followed by standard 3 + 3 cohorts where two dose regimens, weekly versus every three weeks, will be studied in parallel. Expansion cohorts will explore specific tumor types and/or biomarker-selected tumors, based upon the experience during dose escalation. Safety endpoints include dose-limiting toxicities, adverse events, and circulating cytokines. Objective responses will be assessed by RECIST v1.1 for solid tumors and Lugano criteria for lymphoma. Pharmacokinetics and pharmacodynamics will also be evaluated.

"We are particularly pleased to see ALPN-202 enter the clinic," said Mitchell Gold, MD, Alpine’s Chairman and CEO. "ALPN-202 embodies the unique founding concepts of Alpine’s vIgD platform, incorporating tri-functional agonism and antagonism in a single proprietary functional domain. It is now positioned to determine the clinical relevance of localized CD28 costimulation to the immunotherapy of cancer. We look forward to opportunities to report upon its progress in appropriate future settings."

AACR has made the 2020 virtual Annual Meeting presentations freely available. Alpine’s recorded oral presentation of the NEON-1 trial design can be accessed here.

About ALPN-202

ALPN-202 is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor with the potential to improve upon the efficacy of combined checkpoint inhibition while limiting significant toxicities. Preclinical studies of ALPN-202 have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. A phase 1 trial of ALPN-202 in advanced malignancies (NEON-1, NCT04186637) is open for enrollment.

On April 27, 2020 Aeglea BioTherapeutics, Inc. (Nasdaq: AGLE), a clinical-stage biotechnology company developing next-generation human enzyme therapeutics as disruptive solutions for rare and other high-burden diseases, reported a proposed underwritten public offering in which it intends to offer and sell $100 million of shares of its common stock and, in lieu of common stock, to offer and sell to certain investors pre-funded warrants to purchase shares of its common stock (Press release, Aeglea BioTherapeutics, APR 27, 2020, View Source [SID1234556621]). Aeglea expects to grant the underwriters a 30-day option to purchase additional shares of common stock in an amount equal to up to 15% of the securities offered in the public offering. All of the securities are being offered by Aeglea. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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J.P. Morgan Securities LLC, Evercore Group L.L.C. and Piper Sandler & Co. are acting as joint book-running managers in the offering. JonesTrading Institutional Services LLC and Needham & Company, LLC are acting as co-managers.

Aeglea intends to use the net proceeds from the offering, together with its existing cash resources, to advance the clinical development of pegzilarginase through its Phase 3 PEACE trial and BLA submission, advance its Phase 1/2 clinical trial and prepare for a potential Phase 3 trial of ACN00177 for Homocystinuria, and the remainder to fund continued research and development, manufacturing, commercialization infrastructure and for working capital and general corporate purposes.

The securities are being offered by Aeglea pursuant to a registration statement on Form S-3 previously filed and declared effective by the Securities and Exchange Commission (SEC). The offering will be made only by means of the written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying base prospectus may also be obtained, when available, from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, by telephone at (888) 474-0200, or by e-mail at: [email protected]; or Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, Attention: Prospectus Department, by telephone at (800) 747-3924 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities of Aeglea, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 27, 2020 Lexicon Pharmaceuticals, Inc (Nasdaq: LXRX), reported financial results and provided a business update for the three months ended March 31, 2020 (Press release, Lexicon Pharmaceuticals, APR 27, 2020, View Source [SID1234556618]).

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"We achieved 17% growth in XERMELO net sales for the first quarter of 2020 compared to the prior-year period, and we see favorable growth dynamics going forward," said Lonnel Coats, Lexicon’s president and chief executive officer. "We have made good progress on our pipeline, having fully enrolled the first efficacy cohort of 20 patients in the Phase 2 telotristat ethyl study in biliary tract cancer from which we expect top-line data later this year. Importantly, we are steps closer to advancing our next major innovation, LX9211, into a proof-of-concept study in diabetic peripheral neuropathic pain, which we expect to initiate mid-year. Finally, we are making progress on the close-out of the two sotagliflozin outcome studies, SCORED and SOLOIST, which we expect to conclude in the near term."

First Quarter Product and Pipeline Highlights

XERMELO (telotristat ethyl)

•XERMELO U.S. net sales were $7.9 million in the first quarter of 2020.
•Medical record data on XERMELO’s antiproliferative effects were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Symposium in gastrointestinal cancers, showing that, among 200 patients with metastatic neuroendocrine tumors on standard background therapies, the mean tumor size was 0.59 cm smaller (p=0.006) in scans obtained after initiation of XERMELO.
•Medical record data on XERMELO’s antiproliferative effects in patients with carcinoid syndrome presented at the European Neuroendocrine Tumor Society (ENETS) meeting demonstrated that most patients with metastatic neuroendocrine tumors on standard background therapies had no tumor progression at 6, 12 and 18 months following initiation of XERMELO, with a median time to tumor progression (TTP) of 39.8 months. The majority of patients also experienced progression-free survival (PFS) in the period following initiation of XERMELO, with a median PFS of 23.7 months. In addition, in a subset of 22 patients with recorded biomarker data, mean serotonin levels decreased significantly in the period following initiation of XERMELO. Patients also improved on carcinoid syndrome (CS) symptoms, body weight and performance status.
•The Telotristat Ethyl for Advanced Biliary Tract Cancer, or TELE-ABC, study, a Phase 2a clinical study of telotristat ethyl in patients with biliary tract cancer, completed enrollment of 20 patients in the first efficacy cohort.

Sotagliflozin

•In March, Lexicon announced the early close-out of the two long-term outcomes studies of sotagliflozin, SCORED and SOLOIST, that were originally designed to demonstrate benefits in and support labeling for heart failure and chronic kidney disease.

First Quarter 2020 Financial Highlights

Revenues: Revenues for the three months ended March 31, 2020 decreased to $8.0 million from $9.2 million for the corresponding period in 2019, primarily due to a decrease of collaborative revenues, partially offset by an increase in net product revenue. Net product revenues for the three months ended March 31, 2020 consisted of $7.9 million from net sales of XERMELO in the U.S., up 17% from the prior year quarter.

Cost of Sales: Cost of sales related to sales of XERMELO for each of the three months ended March 31, 2020 and 2019 was $0.6 million.

Research and Development (R&D) Expenses: Research and development expenses for the three months ended March 31, 2020 increased to $55.2 million from $12.0 million for the corresponding period in 2019, primarily due to increases in external clinical development costs related to sotagliflozin subsequent to the termination of the alliance with Sanofi.

Selling, General and Administrative (SG&A) Expenses: Selling, general and administrative expenses for the three months ended March 31, 2020 were $14.7 million as compared to $14.1 million for the corresponding period in 2019.

Net Loss: Net loss for the three months ended March 31, 2020 was $66.6 million, or $0.63 per share, as compared to a net loss of $21.8 million, or $0.21 per share, in the corresponding period in 2019. For the three months ended March 31, 2020 and 2019, net income included non-cash, stock-based compensation expense of $4.4 million and $3.4 million, respectively.

Cash and Investments: As of March 31, 2020, Lexicon had $249.1 million in cash and investments, as compared to $271.7 million as of December 31, 2019.

Anticipated Near-Term Milestones

•Mid-2020 – Initiation of the Phase 2 study for LX9211 in diabetic peripheral neuropathic pain
•Q4 2020 – Data from the first efficacy cohort of the Phase 2 study of telotristat ethyl in biliary tract cancer
•2020 – Manuscript publications for XERMELO in carcinoid syndrome diarrhea

Conference Call and Webcast Information

Lexicon management will hold a live conference call and webcast today at 8:00 am EST / 7:00 am CST to review its financial and operating results and to provide a general business update. The dial-in number for the conference call is 888-645-5785 (U.S./Canada) or 970-300-1531 (international). The conference ID for all callers is 9403118. The live webcast and replay may be accessed by visiting Lexicon’s website at www.lexpharma.com/investors. An archived version of the webcast will be available on the website for 14 days.

About XERMELO (telotristat ethyl)

Discovered using Lexicon’s unique approach to gene science, XERMELO (telotristat ethyl) is the first and only approved oral therapy for carcinoid syndrome diarrhea. XERMELO targets tryptophan hydroxylase, an enzyme that mediates the excess serotonin production within metastatic neuroendocrine tumor (mNET) cells. XERMELO is approved in the United States, the European Union and certain additional countries for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. Carcinoid syndrome is a rare condition that occurs in patients living with mNETs and is characterized by frequent and debilitating diarrhea. XERMELO targets the overproduction of serotonin inside mNET cells, providing an additional treatment option for patients suffering from carcinoid syndrome diarrhea.

Lexicon has granted Ipsen an exclusive royalty-bearing right and license to commercialize XERMELO outside of the United States and Japan. We are commercializing XERMELO in the United States and Ipsen is commercializing XERMELO in multiple countries, including the United Kingdom and Germany.

XERMELO (telotristat ethyl) Important Safety Information

•Warnings and Precautions: XERMELO may cause constipation, which can be serious. Monitor for signs and symptoms of constipation and/or severe, persistent, or worsening abdominal pain in patients taking XERMELO. Discontinue XERMELO if severe constipation or severe, persistent, or worsening abdominal pain develops.

•Adverse Reactions: The most common adverse reactions (≥5%) include nausea, headache, increased gamma-glutamyl-transferase, depression, flatulence, decreased appetite, peripheral edema, and pyrexia.
•Drug Interactions: If necessary, consider increasing the dose of concomitant CYP3A4 substrates, as XERMELO may decrease their systemic exposure. If combination treatment with XERMELO and short-acting octreotide is needed, administer short-acting octreotide at least 30 minutes after administering XERMELO.

For more information about XERMELO, see Full Prescribing Information at www.xermelo.com

About Sotagliflozin

Discovered using Lexicon’s unique approach to gene science, sotagliflozin is an oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney. Sotagliflozin is approved in the European Union (EU) for use as an adjunct to insulin therapy to improve blood sugar (glycemic) control in adults with type 1 diabetes with a body mass index ≥ 27 kg/m2, who could not achieve adequate glycemic control despite optimal insulin therapy.