On August 11, 2021 Aileron Therapeutics (NASDAQ:ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported business highlights and financial results for the second quarter ended June 30, 2021 (Press release, Aileron Therapeutics, AUG 11, 2021, View Source [SID1234586335]).

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"Bolstered by a strong balance sheet and a healthy cash runway, we continue to execute against our clinical development strategy to advance selective chemoprotection for patients with p53-mutated cancer, including our initiation in the second quarter of our first randomized, double-blind, placebo-controlled clinical trial of ALRN-6924 for patients with p53-mutated non-small cell lung cancer (NSCLC)," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron.

Dr. Aivado continued, "The findings from this NSCLC trial will inform our late-stage clinical development strategy for ALRN-6924. Nearly 1 million cancer patients across all cancer types each year are diagnosed with p53-mutated cancer in the United States alone, and chemotherapy continues to be a cornerstone of cancer treatment for nearly every patient. As such, we believe that ALRN-6924 has the potential to protect many patients from chemotherapy-induced effects, thereby transforming their quality of life while they undergo chemotherapy and without reducing the effects of chemotherapy against cancer."

Aileron is developing ALRN-6924 to selectively protect healthy cells in patients with cancers that harbor p53 mutations, which are present in over half of all cancer patients, to reduce or eliminate chemotherapy-induced side effects while not interfering with chemotherapy’s attack on cancer cells. This novel concept is known as chemoprotection. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients’ quality of life and help them better tolerate chemotherapy. Enhanced tolerability may lead to fewer dose reductions or delays of chemotherapy, which could result in an improved efficacy of chemotherapy. Given Aileron’s p53 biomarker approach, designed to ensure selective chemoprotection only of healthy cells, coupled with the prevalence of p53-mutated cancers, the company’s strategy is to ultimately pursue a tumor-agnostic label for ALRN-6924 as a chemoprotective agent in p53-mutated cancers.

Second Quarter 2021 Highlights and Recent Updates

Initiated randomized, double-blind, placebo-controlled Phase 1b clinical trial of ALRN-6924 in patients with advanced NSCLC undergoing chemotherapy. Aileron anticipates enrolling a total of 60 patients with advanced p53-mutated NSCLC undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors. Patients enrolled in the NSCLC trial will be randomized 1:1 to receive carboplatin/pemetrexed plus 0.3 mg/kg ALRN-6924 or placebo for at least four 21-day treatment cycles. Components of the primary endpoint are the proportion of treatment cycles free of severe hematological and other toxicities, including Grade ≥ 3 neutropenia, Grade ≥ 3 thrombocytopenia, Grade ≥ 3 anemia, Grade 4 neutropenia and febrile neutropenia, as well as duration of Grade 4 neutropenia. An additional component of the primary endpoint is the proportion of completed treatment cycles without chemotherapy dose reduction or without the use of growth factors or transfusions. Other endpoints include the proportion of patients with National Cancer Institute Common Terminology Criteria Adverse Events Grade 3/4 treatment-emergent adverse events, quality of life, overall response rate, and progression-free survival.

Aileron anticipates reporting first interim safety data from the trial late in the fourth quarter of 2021 and topline results in mid-2022.
Company to present final data from ALRN-6924 SCLC study and initial data from Healthy Volunteer Study at two upcoming scientific congresses. Aileron has had abstracts accepted for presentation at the International Society for Experimental Hematology (ISEH) 2021 Virtual Scientific Meeting, being held August 25-28, 2021, and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021, being held September 16-21, 2021. At these congresses, Aileron will present final data from its Phase 1b study of ALRN-6924 in patients with SCLC undergoing chemotherapy with second-line topotecan. This presentation follows Aileron’s October 2020 presentation of data from its Phase 1b clinical trial of ALRN-6924 in SCLC demonstrating clinical proof-of-concept that treatment with ALRN-6924 resulted in a protective effect against neutropenia, thrombocytopenia and anemia in patients with p53-mutated SCLC treated with topotecan. A link to the SCLC presentation from October 2020 can be found here.

Aileron will also present initial data at both meetings from its ongoing Healthy Volunteer Study, which is evaluating ALRN-6924’s induction of p21-induced cell cycle arrest in healthy, normal bone marrow cells and other cell types in healthy volunteers receiving ALRN-6924. p53 upregulates the expression of p21, a known inhibitor of cell cycle. The Healthy Volunteer Study, therefore, is designed to characterize the time to onset, magnitude and duration of p21-induced cell cycle arrest in human bone marrow relative to ALRN-6924. The ultimate aim of the study is to develop a universal dosing regimen for ALRN-6924 for use as a chemoprotection agent across a range of chemotherapies and p53-mutated tumor indications.
Presented poster at 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, co-authored by Foundation Medicine, Inc., demonstrating rarity of longitudinal changes in p53 mutation status. In June 2021, Aileron presented a poster co-authored by Foundation Medicine, Inc., entitled, "Frequency of longitudinal changes in TP53 mutation status from gene sequencing of serial tumor biopsies from a large cohort of cancer patients," at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. The companies examined approximately 16,500 samples arising from repeat biopsies from more than 7,800 patients across a spectrum of cancer types and over an average interval of 11 months and up to 23 months between biopsies. The analysis found that in nearly all of the biopsies evaluated (97%), an initial p53-mutant diagnosis was maintained in subsequent biopsies, regardless of cancer type, primary tumor versus metastases, or time period between subsequent biopsies.
Second Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and investments on June 30, 2021 were $59.5 million, compared to $13.8 million at December 31, 2020. The company expects, based on its current operating plan, that its existing cash, cash equivalents and investments will fund operations into the second half of 2023.

Research and Development (R&D) Expenses: R&D expenses for the quarter ended June 30, 2021 were $3.9 million, compared to $2.5 million for the quarter ended June 30, 2020. The increase of $1.4 million primarily results from increased spending for clinical development of ALRN-6924 for the company’s Phase 1b clinical trial in patients with advanced NSCLC and the study of ALRN-6924 in healthy volunteers. The company also increased its spending on ALRN-6924 manufacturing costs, employee-related costs and non-clinical research costs while decreasing facility-related spending.

General and Administrative (G&A) Expenses: G&A expenses for the quarter ended June 30, 2021 were $2.2 million compared to $1.9 million for the quarter ended June 30, 2020. Increased G&A expenses were primarily the result of higher employee-related costs partially offset by lower facility costs.

Net Loss: Net loss for the quarter ended June 30, 2021 was $5.7 million, compared to $4.4 million for the corresponding quarter in 2020. The basic and diluted net loss per share for the second quarter of 2021 was $0.06 compared to $0.14 for the second quarter of 2020. The change in basic and diluted net loss per share is primarily a result of increased shares outstanding in connection with sales of common stock during the first quarter of 2021.

On August 11, 2021 Personal Genome Diagnostics Inc. (PGDx) reported the publication of a research paper in The Oncologist, titled "Validation of a ctDNA-based next-generation sequencing assay in a cohort of solid tumor patients: a proposed solution for decentralized plasma testing," which assessed the performance of the company’s elio plasma resolve assay (Press release, Personal Genome Diagnostics, AUG 11, 2021, View Source [SID1234586352]). This is the first study validating that a decentralized plasma-based next-generation sequencing (NGS) test can detect microsatellite instability (MSI) status along with the comprehensive landscape of sequence and structural alterations encountered across solid tumors.

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The study, from Weill Cornell Medicine’s Englander Institute for Precision Medicine, profiled DNA from matched tissue and plasma samples from 75 cancer patients and showed that elio plasma resolve detected 77% of sequence alterations, amplifications, and fusions that were found in metastatic samples compared to 45% of those alterations found in the primary tumor samples. There was 87% agreement for MSI status between elio plasma resolve and tumor tissue results. In 3 cases, the assay’s identification of MSI-high circulating tumor DNA (ctDNA) correlated with response to immunotherapy. In addition, the PGDx kit revealed an FGFR2 amplification that was not detected in tumor tissue from a patient with metastatic gastric cancer.

"We are elated to see that in this study, elio plasma resolve demonstrated the comprehensive ability to identify MSI-high DNA samples from cancer patients," said Megan Bailey, Chief Executive Officer of PGDx. "We believe these results show tremendous potential for elio plasma resolve and the overall benefits of cell-free DNA testing, and we are hopeful that this testing can become routine practice in the treatment of cancer."

PGDx currently offers three pan-cancer NGS kitted solutions – elio tissue complete, an FDA cleared kit, elio plasma complete, a comprehensive liquid biopsy solution, and elio plasma resolve, which has received FDA breakthrough device designation – that provide researchers and clinicians with the ability to identify biomarkers and profile tumors through advanced genomic sequencing within their own hospital systems and laboratories. elio plasma resolve is designated for research use only in the U.S. and with a CE-IVD mark in Europe.

On August 11, 2021 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the second quarter and year-to-date for the period ended June 30, 2021 (Press release, Navidea Biopharmaceuticals, AUG 11, 2021, View Source [SID1234586336]).

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"The Company is prepared and looking forward to our meeting with the U.S. Food and Drug Administration ("FDA") on September 1," said Mr. Jed A. Latkin, Chief Executive Officer of Navidea. "We remain laser focused on a positive meeting and a successful launch to the NAV3-33 trial. Navidea is also extremely excited to now have a full 7-member board with the appointments of Amit Bhalla, Alex Cappello and John K. Scott, Jr. to the board."

Second Quarter 2021 Highlights and Subsequent Events

Scheduled an End-of-Phase 2 Type B meeting with the FDA to discuss its ongoing program in Rheumatoid Arthritis ("RA") and advancement to the pivotal Phase 3 trial. The meeting will take place on September 1, 2021, via conference call.
Achieved study closeout in the Company’s NAV3-31 Phase 2b study.
Opened the first U.S. site, Northwestern University, as well as the primary U.K. site, Queen Mary University of London, for enrollment in the Company’s NAV3-32 Phase 2b trial comparing Tc99m tilmanocept imaging to histopathology of joints of patients with active RA. A second U.S. site, Attune Health Research, will be opened on August 13, 2021.
Enrolled over 115 subjects in the Company’s NAV3-35 Phase 2b study, "Development of a Normative Database for Rheumatoid Arthritis (RA) Imaging with Tc99m Tilmanocept." Expected total enrollment for this two-arm trial will be 135 participants.
Completed enrollment in the investigator-initiated Phase 2 trial being run at the Massachusetts General Hospital evaluating Tc99m tilmanocept uptake in atherosclerotic plaques of HIV-infected individuals.
Announced the granting of a National Institutes of Health ("NIH") award to the University of California San Diego School of Medicine for the proposal entitled, "Renal Molecular Imaging of Mesangial Cell Function with Tc-99m-Tilmanocept." The award (Project Number: 1R01DK127201-01), from the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH, was granted to Co-Principal Investigators UC San Diego faculty Carl Hoh, MD and David Vera, PhD, of the Department of Radiology, and Charles Ginsberg, MD, MAS, of the Department of Medicine, Division of Nephrology.
Results from the Company’s preclinical studies of its targeted cancer immunotherapeutic agent were presented as a poster at the New York Academy of Science’s ("NYAS") Frontiers in Cancer Immunotherapy Symposium 2021. The poster is titled, "Targeted Delivery of Doxorubicin (DOX) to Tumor Associated Macrophages (TAMs) Beneficially Alters the Tumor Immune Microenvironment and Synergizes the Activity of Anti-CTLA4."
Announced that the U.S. Patent and Trademark Office ("USPTO") issued to Navidea U.S. patent 11,007,272, entitled "Compounds and Methods for Diagnosis and Treatment of Viral Infections," with protection to October 7, 2037.
Converted the provisional patent application "Synthesis of Uniformly Defined Molecular Weight Mannosylated Dextrans and Derivatives Thereof" to an A1 application on July 9, 2021.
Appointed Amit Bhalla to the Company’s Board of Directors. Mr. Bhalla brings a wealth of financial experience and over 20 years of pharmaceutical experience to the board.
Appointed John K. Scott, Jr. and Alex Cappello to the Board of Directors. Mr. Scott is the Company’s largest shareholder and Mr. Cappello brings over 30 years of banking and public board experience to the Company.
Announced that on June 23, 2021, Vice Chancellor Joseph Slights of the Court of Chancery of the State of Delaware (the "Court") ruled in favor of Navidea’s wholly-owned subsidiary, Macrophage Therapeutics, Inc. ("MT") and against its former CEO, Dr. Michael Goldberg, finding that Dr. Goldberg breached his fiduciary duties to MT. In addition, the Court denied Dr. Goldberg’s motion to hold MT’s directors and CEO in contempt, denied Dr. Goldberg’s motion to dismiss the lawsuit against him, and granted MT’s motion to dismiss Dr. Goldberg’s petition to remove MT’s board members.
Michael Rosol, Ph.D., Chief Medical Officer for Navidea, said, "The clinical research team continues to work diligently to advance the technology in key disease areas, with an emphasis on our RA program. We are preparing for our September discussion with the FDA over the results of the completed NAV3-31 Phase 2b trial as well as our proposed plan for the Phase 3 study. We continue to prepare for initiation of the Phase 3 and have opened up key sites for enrollment into the NAV3-32 Phase 2b trial comparing tilmanocept imaging to synovial tissue biopsy samples of RA patients. Concurrent with all of this, we continue to make exciting progress in our therapeutics pipeline, and we expect to continue to advance these towards the clinic."

Financial Results

Total net revenues for the second quarter of 2021 were $261,000, compared to $271,000 for the same period in 2020. Total net revenues for the first six months of 2021 were $385,000, compared to $427,000 for the same period in 2020. The decrease was primarily due to decreased grant revenue related to Small Business Innovation Research grants from the National Institutes of Health supporting Manocept development, offset by receipt of reimbursement from Cardinal Health 414, LLC of certain research and development ("R&D") costs and the partial recovery of debts previously written off in 2015.
R&D expenses for the second quarter of 2021 were $1.5 million, compared to $1.3 million in the same period in 2020. R&D expenses for the first six months of 2021 were $2.7 million, compared to $2.3 million in the same period in 2020. The increase was primarily due to net increases in drug project expenses, including increased Manocept diagnostic and therapeutic development costs. The net increase in research and development expenses also included increased regulatory consulting expenses offset by decreased employee compensation including incentive-based awards.
Selling, general and administrative ("SG&A") expenses for the second quarter of 2021 were $1.4 million, compared to $1.3 million in the same period in 2020. SG&A expenses for the first six months of 2021 were $3.7 million, compared to $3.2 million in the same period in 2020. The net increase was primarily due increased consulting services related to preparing for European distribution of Tc99m tilmanocept, increased employee compensation including incentive-based awards, increased insurance cost, increased director fees related to additional board members, increased general office expenses, increased travel costs and increased European license fees, offset by decreased legal and professional services and decreased investor relations costs.
Navidea’s net loss attributable to common stockholders for the second quarter of 2021 was $2.7 million, or $0.09 per share, compared to $2.4 million, or $0.11 per share, for the same period in 2020. Navidea’s net loss attributable to common stockholders for the first six months of 2021 was $5.6 million, or $0.20 per share, compared to $5.1 million, or $0.24 per share, for the same period in 2020.
Navidea ended the second quarter of 2021 with $7.1 million in cash and cash equivalents.
Conference Call Details

Investors and the public are invited to dial into the earnings call through the information listed below, or participate via the audio webcast on the company website. Participants who would like to ask questions during the question and answer session will be prompted by the moderator, who will provide instructions.

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.

On August 11, 2021 Advanced Chemotherapy Technologies (ACT), Inc., a clinical-stage drug delivery company, reported that it has been awarded a Phase IIb Small Business Innovation research (SBIR) grant expected to total $4 million over two years from the National Cancer Institute, part of the National Institutes of Health (Press release, Advanced Chemotherapy Technologies, AUG 11, 2021, View Source [SID1234586353]). The grant, in combination with prior financing, supports development of the company’s ACT-IOP-003 local drug delivery system for the treatment of locally advanced non-resectable and borderline resectable pancreatic cancer.

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Pancreatic cancer is a devastating disease with 5-year survival rates of only 10%. New treatment modalities are desperately needed and ACT is developing the ACT-IOP-003 system for the targeted delivery of the FDA-approved chemotherapy treatment gemcitabine. ACT-IOP-003 enables the delivery of significantly higher concentrations directly to the tumor than achievable in systemic delivery, while also minimizing the systemic exposure and toxicity. This approach offers three major advantages over traditional systemic chemotherapy: (1) superior delivery of chemotherapy to the targeted tumor cells that are often shrouded in stroma within growing tumors, greatly increasing the amount of drug to treat the growing tumor, (2) tumor shrinkage that can enable surgical resection, the only curative treatment for pancreatic cancer, and (3) greatly decreased systemic toxicity so that the patient can better tolerate conventional approaches to their treatment.

William Daunch PhD., ACT’s Chief Technology Officer will serve as the Principal Investigator on the grant. Dr. Daunch says, "We are thrilled and encouraged that NCI has chosen to award us this highly competitive Phase IIb grant. It demonstrates the NIH’s positive recognition of the work we completed in our earlier phases, as well as their continued confidence in our program to accelerate this potentially life extending treatment to patients."

NIH sponsored grant programs are an integral source of capital for early-stage U.S. small businesses that are creating innovative technologies to improve human health. These programs help small businesses break into the federal research and development arena, create life-saving technologies, and stimulate economic growth. ACT is honored to be a recipient of this competitive award from the NIH/NCI and looks forward to advancing treatment for pancreatic cancer patients and expanding its local drug delivery technology in new indications

On August 11, 2021 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted therapies for rare and difficult to treat cancers, reported it will present data from one planned clinical trial and one completed preclinical study evaluating its lead investigational drug, Rhenium-186 Nanoliposome (186RNL), for the treatment of leptomeningeal metastases (LM) (Press release, Cytori Therapeutics, AUG 11, 2021, View Source [SID1234586310]). The data will be presented at the Third Annual Conference on Brain Metastases hosted by the Society for Neuro-Oncology (SNO), being held virtually August 19-20, 2021.

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Data from both studies will be presented as electronic posters (ePosters) by Andrew J. Brenner, M.D., Ph.D., Associate Professor of Medicine, Neurology, and Neurosurgery at The University of Texas, and principal investigator, and will be viewable to meeting attendees beginning at the start of the conference on Thursday, August 19 at 11:00 am EDT. The accepted abstracts are currently available in the Neuro-Oncology Advances Journal. Details of both are as follows:

LMD-13: "ReSPECT-LM: Maximum tolerated dose, safety, and efficacy of intraventricular Rhenium-186 Nanoliposome ( 186 RNL) for leptomeningeal metastases"
Data from the ongoing U.S. multi-center ReSPECT-GBM Phase 1 dose-finding clinical trial in adults with recurrent glioblastoma (NCT01906385) demonstrate that the mean absorbed dose of 186RNL to the tumor when coverage was 75% or greater (n=10) was 392 Gy (CI 306 – 478). Thus far, the therapy has been well tolerated with one possible treatment-related serious adverse event, cerebral edema, that resolved after steroid treatment.

In addition, this abstract details a proposed two-part clinical trial for patients with leptomeningeal metastases (LM). Part 1 will enroll up to 21 subjects to characterize the safety and tolerability of a single dose of 186RNL administered intraventricularly via an Ommaya reservoir and identify a maximum tolerated dose (MTD) / maximum feasible dose (MFD) for future studies, and Part 2 will independently evaluate 186RNL in two different cohorts. Cohort A will enroll up to 20 subjects with a diagnosis of LM from primary breast cancer. Cohort B will enroll up to 20 subjects with a diagnosis of LM from primary non-small cell lung cancer. The primary endpoint is to estimate the anti-tumor activity of 186RNL as a single agent. The full abstract can be found here: View Source

LMD-14: "Preclinical safety and activity of intraventricular Rhenium-186 Nanoliposome ( 186 RNL) for leptomeningeal metastases"
As part of this preclinical safety and activity study, researchers concluded that the intraventricular delivery of 186RNL is well tolerated and improves animal survival at two weeks in a rat model of LM. The full abstract can be found here: View Source

Copies of each poster will be made available under the Presentations tab of the Investors section of the Company’s website when presentations go live at www.plustherapeutics.com.

LM are a rare but typically fatal complication of advanced cancer that affects the fluid-lined structures of the central nervous system and are diagnosed in approximately five percent of patients with metastatic cancer. With survival measured in weeks to months, novel approaches are needed that can both improve quality and quantity of life. 186RNL permits the selective delivery of beta-emitting radiation of high specific activity directly to the tumor.