On March 21, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the discontinuation of ORIC-101 and also reported financial results and operational updates for the quarter and year ended December 31, 2021 (Press release, ORIC Pharmaceuticals, MAR 21, 2022, View Source [SID1234610470]). The company conducted planned interim analyses of two Phase 1b studies and concluded that ORIC-101 did not demonstrate sufficient clinical activity to warrant further development.

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"We are disappointed in the outcome of the ORIC-101 studies in combination with nab-paclitaxel in various solid tumors and in combination with enzalutamide in metastatic prostate cancer, two late-line patient populations for whom limited treatment options exist today. We believe both studies were well designed, allowing us to thoroughly and efficiently answer an important clinical question. With this decision to discontinue ORIC-101 development, we would like to thank the investigators, site staff, the ORIC team, and most importantly, patients and families who participated in the trials," said Pratik S. Multani, MD, chief medical officer.

"We’ve always been committed to rapid, data driven decision making and allocating resources efficiently and prudently," said Jacob M. Chacko, MD, chief executive officer, "We intentionally built a diverse pipeline of differentiated programs, which includes our Phase 1b single agent trials for ORIC-533, our orally bioavailable CD73 inhibitor, ORIC-114, our brain penetrant EGFR/HER2 inhibitor, and ORIC-944, our embryonic ectoderm development (EED) inhibitor. We expect to report initial data from each study in the first half of 2023. As a result of the ORIC-101 discontinuation, we project our cash runway to extend into the second half of 2024, well beyond the planned initial data disclosures from these three clinical programs."

Fourth Quarter 2021 and Other Recent Highlights

ORIC-101: Glucocorticoid Receptor Antagonist

Based on interim analyses from the two Phase 1b studies, ORIC-101 did not demonstrate sufficient clinical activity and, therefore, the company has discontinued further development.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with enzalutamide enrolled 28 patients at the recommended phase 2 dose (RP2D) with metastatic prostate cancer progressing on enzalutamide. The RP2D was well tolerated with a safety profile consistent with previously reported results. ORIC-101 in combination with enzalutamide did not translate into a meaningful clinical benefit, with a median progression-free survival (PFS) in the target patient population of 3.7 months.

The dose expansion portion of the Phase 1b clinical trial of ORIC-101 in combination with nab-paclitaxel enrolled 61 patients at the RP2D across four cohorts: pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, triple negative breast cancer (TNBC), and other advanced solid tumors. The RP2D was well tolerated with a safety profile consistent with previously reported results. There were no objective responses in the PDAC cohort (n=21) and there was one confirmed partial response in the ovarian cancer cohort (n=13). There was no meaningful clinical benefit based on median PFS across all cohorts (PDAC: 1.9 months, and ovarian cancer: 2.2 months).

ORIC-533: CD73 Inhibitor
ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73 and has demonstrated more potent adenosine inhibition in preclinical studies compared to an antibody approach and other small molecule inhibitors of the adenosine pathway.

Ex vivo human data supporting the therapeutic potential of single agent ORIC-533 in multiple myeloma were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting.
Single agent activity in an autologous bone marrow mononuclear assay system from multiple myeloma patients showed CD73 inhibition compared favorably to approved therapies for the treatment of multiple myeloma, including lenalidomide, bortezomib and daratumumab.
A Phase 1b trial with ORIC-533 as a single agent in multiple myeloma is enrolling patients and initial data are expected to be reported in the first half of 2023.

ORIC-114: EGFR/HER2 Inhibitor
ORIC-114 is a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations.

Compelling brain exposure and antitumor activity of ORIC-114 in preclinical studies of HER2-positive breast cancer were presented at AACR (Free AACR Whitepaper)-NCI-EORTC.
Head-to-head data in an EGFR exon 20 NSCLC xenograft model were disclosed demonstrating good tolerability and improved efficacy, including a 90% complete response rate, with ORIC-114 versus multiple clinical stage exon 20 inhibitors.
The Clinical Trial Application (CTA) for ORIC-114 was filed in the fourth quarter of 2021 and was cleared by the regulatory authorities of the Republic of Korea in the first quarter of 2022.
A Phase 1b trial with ORIC-114 as a single agent has been initiated and will enroll patients with advanced solid tumors with EGFR or HER2 exon 20 alterations or HER2 amplification and will allow patients with CNS metastases that are either treated or untreated but asymptomatic. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
ORIC-944: PRC2 Inhibitor
ORIC-944 is a potent and selective allosteric inhibitor of polycomb repressive complex 2 (PRC2) that targets its regulatory embryonic ectoderm development (EED) subunit and has demonstrated single agent efficacy in multiple enzalutamide-resistant prostate cancer models in preclinical studies.

The IND for ORIC-944 was cleared by the FDA in the fourth quarter of 2021.
A Phase 1b trial with ORIC-944 as a single agent will enroll patients with metastatic prostate cancer. The company expects to report initial Phase 1b data from this trial in the first half of 2023.
PLK4 Inhibitor Program
In March, the company announced a small molecule therapeutic program intended to address a mechanism of innate resistance found in a subset of breast cancers, specifically a synthetic lethal interaction of polo-like kinase 4 (PLK4) inhibition in tumors bearing a TRIM37 DNA amplification. Breast cancer models as well as other tumor models with this TRIM37 amplification have a key tumor dependency on PLK4 and our therapeutic approach is to selectively inhibit this enzyme.

Corporate
In November 2021, the company appointed Angie You, PhD, to its board of directors. Dr. You was most recently CEO of Amunix Pharmaceuticals, which was acquired by Sanofi, and brings broad experience spanning venture capital, business development and public company leadership roles.

Anticipated Program Milestones

ORIC anticipates the following upcoming milestones:

ORIC-533: Initial Phase 1b data in 1H 2023
ORIC-114: Initial Phase 1b data in 1H 2023
ORIC-944: Initial Phase 1b data in 1H 2023
Fourth Quarter and Full year 2021 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $280.4 million as of December 31, 2021, and with the discontinuation of ORIC-101, the company expects its cash runway to be extended into the second half of 2024.

R&D Expenses: Research and development (R&D) expenses were $16.7 million for the three months ended December 31, 2021, compared to $12.1 million for the three months ended December 31, 2020, an increase of $4.6 million. For the year ended December 31, 2021, R&D expenses were $56.9 million compared to $35.9 million for the same period of 2020, an increase of $20.9 million. The increases for the 2021 periods were primarily driven by an increase in external expenses related to the advancement of ORIC-101, ORIC-533 and our other product candidates, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.7 million and $2.9 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively.

G&A Expenses: General and administrative (G&A) expenses were $6.1 million for the three months ended December 31, 2021, compared to $4.3 million for the three months ended December 31, 2020, an increase of $1.8 million. For the year ended December 31, 2021, G&A expenses were $22.0 million compared to $13.4 million for the same period in 2020, an increase of $8.6 million. These increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $1.1 million and $4.6 million for the three and twelve months ended December 31, 2021, as compared to the same periods in 2020, respectively, and higher costs related to operating as a public company.
Webcast and Conference Call

ORIC will host a conference call and webcast today at 5:00 p.m. ET. To participate in the conference call, please dial (833) 651-0991 (domestic) or (918) 922-6080 (international) and refer to conference ID 8637367. A live webcast and audio archive of the conference call will be available through the investor section of the company’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

On March 21, 2022 Oasmia Pharmaceutical AB, an oncology-focused specialty pharmaceutical company, and Lonza, a global development and manufacturing partner to the pharma, biotech and nutrition industries, reported that the companies have signed a large-scale manufacturing agreement for the main drug intermediate in the supply of clinical material for its investigational drug candidate, Cantrixil (Press release, Oasmia, MAR 21, 2022, View Source [SID1234610469]).

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Cantrixil, an intraperitoneally administered drug in development for the treatment of late-stage ovarian cancer, was licensed by Oasmia from the Australian pharmaceutical company Kazia in 2021, having successfully completed a Phase I trial. Ovarian cancer is one of the most aggressive cancers and is difficult to treat in advanced stages. The Phase I study of Cantrixil demonstrated the potential for it to provide prolonged survival in advanced ovarian cancer by inducing ovarian cancer stem cells’ death and sensitizing cancer cells to standard chemotherapy. Oasmia is now preparing for the initiation of a Phase II trial of Cantrixil in advanced ovarian cancer.

Under the terms of the agreement, Lonza will provide kilogram-scale synthesis, purification, and stability testing of Cantrixil, and deliver cGMP batches of drug substance for clinical supply. Oasmia will leverage Lonza’s extensive experience and expertise in manufacturing highly-potent API (HPAPI). The drug substance will be manufactured at Lonza’s recently expanded production facility at Nansha, China. The manufacturing is expected to begin later in March 2022.

Kai Wilkinson, Chief Technical Officer at Oasmia, commented: "We are excited to have partnered with Lonza, a global leader in drug manufacturing. The manufacture of Cantrixil is planned to be performed in three steps and this agreement is the first and most crucial step in us securing the clinical drug supply for its development."

Christian Dowdeswell, VP and Global Head, Commercial Development – Small Molecules, Lonza, added: "Our team has extensive experience with supporting the development and manufacture of challenging molecules. We are looking forward to collaborating with Oasmia to advance this promising drug candidate in the clinic."

On March 21, 2022 Diffusion Pharmaceuticals Inc. (NASDAQ: DFFN) ("Diffusion" or the "Company"), an innovative biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most, reported financial results for 2021 and provided a business update (Press release, Diffusion Pharmaceuticals, MAR 21, 2022, View Source [SID1234610467]).

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Corporate Strategy and Events

Business and financial highlights during 2021 and 2022 year-to-date include:

Declared Lead Development Program: The Company announced its intent to develop its novel, oxygen enhancing therapeutic, Trans Sodium Crocetinate ("TSC"), as an adjunct to standard of care therapy for hypoxic solid tumors in November 2021 ("Hypoxic Solid Tumor Program").

Strengthened Balance Sheet: In February 2021, the Company raised approximately $34.5 million in gross proceeds through an up-sized, follow-on public offering of its common stock with proceeds to be used to fund research and development efforts for the TSC oxygenation trials ("Oxygenation Trials") and corporate expenses. As of December 31, 2021, the Company reported a total of $37.3 million in cash and cash equivalents. As of March 18, 2022, the Company expects cash resources to fund operations through 2023.

Board Updates: Jane Hollingsworth appointed as new Board Chair in June 2021. Diana Lanchoney, M.D., and Eric Francois also elected to the Company’s board of directors in June 2021.

"We are pleased with the progress we achieved in 2021. We executed our corporate, clinical, and regulatory strategies, accelerating development of our lead product candidate, TSC. The capital we raised in the first half of 2021 allowed us to design and execute critical clinical trials to assess TSC’s therapeutic potential in treating hypoxia-related conditions using three unique short-term experimental clinical models of oxygenation," said Robert Cobuzzi, Jr., Ph.D., President and Chief Executive Officer of Diffusion.

Dr. Cobuzzi continued, "We believe the hard work demonstrated by our team in 2021 has laid a solid foundation for Diffusion’s success in 2022. The initiation of our Altitude and ILD-DLCO trials in the last quarter of 2021 represented a significant inflection point on the route to achieving the goal of demonstrating TSC’s potential to enhance the body’s ability to deliver oxygen to areas where it is needed most and potentially provide a novel treatment option for a variety of conditions complicated by hypoxia. Moreover, in late 2021 we announced our intent to design and execute a clinical program to support the use of TSC as an adjunct treatment of hypoxic solid tumors as the next step in our efforts to realize TSC’s potential. We believe targeting hypoxic solid tumors is appropriate for TSC given the significant unmet medical need, the compelling preclinical and clinical data accumulated to date, and the current, intravenous formulation of TSC. The team has been working closely with our advisors to design a Phase 2 study that we believe, if successful, will help patients and enhance shareholder value."

Clinical Trial Execution & Strategy

TCOM Trial: In March 2021, the Company completed enrollment and dosing of all participants in its Phase 1 trial of TSC utilizing a transcutaneous oxygen monitoring ("TCOM") device to evaluate the pharmacodynamic effects of TSC on peripheral tissue oxygenation in healthy, normal volunteers. As reported in June 2021, the topline results of the study showed TSC was safe and tolerable at all doses tested with no serious adverse events or dose-limiting toxicities. Furthermore, the Company announced that a positive trend in peripheral tissue oxygenation was observed among participants treated with TSC when compared to placebo-treated participants. This trend persisted through the one-hour, post-dosing measurement period. The Company believes the data from the TCOM Trial validate the thesis that TSC enhances oxygenation without causing hyperoxygenation. The data from the TCOM Trial have guided the design of the two additional Oxygenation Trials, as well as the design of the Hypoxic Solid Tumor Program.

Altitude Trial: In November 2021, Diffusion announced the dosing of the first participants in the Altitude Trial which was designed to evaluate the effects of TSC in normal healthy volunteers subjected to incremental levels of physical exertion while exposed to hypoxic and hypobaric conditions, or "simulated altitude." Due to enrollment delays experienced during early 2022 related to the omicron variant wave of the COVID-19 pandemic, the Company now anticipates completing dosing in the second quarter of 2022 and topline results are expected to be reported within one to two months of study completion.

ILD-DLCO Trial: Subsequent to receiving Investigational New Drug application clearance from the U.S. Food and Drug Administration ("FDA") in the third quarter of 2021, the Company announced the dosing of the first patient in the Phase 2 ILD-DLCO Trial in December 2021. The ILD-DLCO Trial was designed to evaluate the effects of TSC on carbon monoxide uptake through the lungs ("DLCO") and into the bloodstream of interstitial lung disease ("ILD") patients. DLCO measurement is used in the study as a surrogate measure of oxygen transfer efficiency, or uptake, from the alveoli of the lungs through the plasma, and onto hemoglobin within red blood cells. The Company intends to evaluate the effect of TSC on lung function as measured by DLCO, as well as distance covered in a standard six-minute walk test. Due to enrollment delays experienced during early 2022 related to the omicron variant wave of the COVID-19 pandemic, the effect of the omicron variant on patients with pulmonary diseases such as ILD, and staffing issues at the facilities where the ILD-DLCO Trial is being conducted, the Company now anticipates dosing to be completed by the middle of 2022, with topline results reported within two months of study completion.

Hypoxic Solid Tumor Treatment: In November 2021, based on the available preclinical and clinical data and the significant unmet medical need, including the TCOM and COVID-19 Trial results, the Company announced its intent to focus its near-term efforts on evaluating TSC as an adjunct to standard of care in the treatment of hypoxic solid tumors as a first indication. Solid tumors, which comprise approximately 90% of all adult cancers, are often affected by hypoxia, leading to treatment resistance, metastasis, and worse prognoses. Following, among other things, analyses and discussions with the Company’s oncology-focused SAB members and other external advisors over the last several months, Diffusion believes they have the necessary data to support the design and initiation of an appropriate Phase 2 trial as the first study in the Hypoxic Solid Tumor Program. The Company intends to file the study protocol with the FDA and expects to commence the trial in the second half of 2022, subject to FDA feedback and the availability of clinical drug supply.

2021 Financial Results

Diffusion had cash and cash equivalents of $37.3 million as of December 31, 2021, compared with $18.5 million as of December 31, 2020. Net cash used in operating activities during 2021 was $14.5 million, compared with $13.6 million used during 2020.

Research and development expenses were $8.5 million for 2021, compared with $9.4 million for 2020. The decrease was primarily attributable to lower project spending due to the completion and/or wind-down of the Company’s clinical studies evaluating TSC in COVID-19, glioblastoma multiforme brain cancer, and stroke.

General and administrative expenses were $7.4 million for 2021, compared with $6.4 million for 2020. The increase was primarily driven by increased headcount resulting in higher compensation expense and other costs associated with the hiring of new employees, as well as an increase in expense related to consulting services.

In 2021, the Company also recognized a non-recurring $8.6 million non-cash impairment charge related to the write down of its DFN-529 IPR&D asset.

On March 21, 2022 MaaT Pharma (EURONEXT: MAAT – the "Company"), a French clinical-stage biotech and a pioneer in the development of microbiome-based ecosystem therapies dedicated to improving survival outcomes for patients with cancer, reported the implementation of a liquidity agreement with Kepler Cheuvreux to enhance the liquidity of the Maat Pharma shares admitted to trading on Euronext Paris (Press release, MaaT Pharma, MAR 21, 2022, View Source [SID1234610466]).

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The implementation of this liquidity agreement, pursuant to the authorization granted by the resolution of the General Meeting, will be carried out in accordance with the legal framework in force, and more particularly to the provisions of Regulation (EU) No. 596/2014 of the European Parliament and of the Council of April 16, 2014 on market abuse (MAR), Commission Delegated Regulation (EU) 2016/908 of February 26, 2016 supplementing Regulation (EU) No. 596/2014 of the European Parliament and of the Council with regulatory technical standards on the criteria, procedure and requirements for the establishment of an admitted market practice and the requirements for maintaining, discontinuing or modifying its conditions of admission, Articles L. 225-209 et seq. of the French Commercial Code and AMF decision no. 2021-01 of June 22, 2021, applicable as of July 1, 2021.

The following resources will be allocated to the liquidity account:

200,000 euros
The execution of the liquidity contract could be suspended under the conditions set out in Article 5 of AMF Decision 2021-01 of 22 June 2021.

The liquidity contract will be implemented as of March 22, 2022, and may be terminated:

at any time by MaaT Pharma without notice
at any time by Kepler Cheuvreux, subject to thirty (30) calendar days’ notice
without notice and without formality if the shares are transferred to another stock market

On March 21, 2022 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported that it will present a poster on the company’s anti-CD27 agonist antibody program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place April 8-13, 2022 onsite in New Orleans, LA and online (Press release, Kineta, MAR 21, 2022, View Source;utm_medium=rss&utm_campaign=kineta-to-present-poster-on-anti-cd27-agonist-antibody-program-at-the-aacr-annual-meeting-2022 [SID1234610465]). Thierry Guillaudeux, PhD, EVP Research and Development at Kineta, will be presenting new preclinical data on the company’s anti-CD27 agonist antibodies in development for the treatment of blood cancers and solid tumors.

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Presentation Details

Title: CD27 a new immuno-oncology target shaping innate and adaptive anti-tumor immune responses
Abstract Number: 5588
Presenter: Thierry Guillaudeux, PhD
Session Type: In-Person and e-Poster Presentation
Session Title: Therapeutic Antibodies 3
Session Time: April 13, 2022 9:00AM – 12:30PM Central Time
Location: Poster Section 39

CD27 is a clinically validated drug target. It is a member of the TNF receptor superfamily and plays a critical role in T-cell activation by providing a co-stimulatory signal together with its ligand CD70. CD27 is highly expressed on naïve T cells and also provides a co-stimulatory signal for NK cell activation. Kineta has developed a diverse set of anti-CD27 agonist antibodies. They are fully human monoclonal antibodies (mAbs) that demonstrate low nM binding affinity to CD27 in humans. In preclinical studies, Kineta’s selected lead anti-CD27 agonist mAbs induce T cell proliferation, NK activation and secretion of cytokines involved in T cell priming and recruitment, demonstrating the ability to potentiate new anti-tumor responses. Kineta is in the final stage of lead selection and plans to nominate a clinical candidate in mid-2022.