On January 13, 2021 Adastra Pharmaceuticals, Inc., a biopharmaceutical company focused on the development of first-in-class therapeutics for the treatment of cancer, reported the completion of the Phase 1b clinical trial conducted by the NCI with its lead clinical candidate zotiraciclib (ZTR/TG02), a potent oral cyclin-dependent kinase 9 (CDK9) inhibitor (Press release, Adastra Pharmaceuticals, JAN 13, 2021, View Source [SID1234573983]). The trial investigated the safety and efficacy of ZTR, in combination with temozolomide (TMZ), in patients with recurrent high-grade gliomas.

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The Phase 1b trial exceeded or met the prespecified trial endpoint of progression-free survival (PFS) and provided a recommended dosing of ZTR. In the subset of patients who had isocitrate dehydrogenase (IDH) mutated tumors, the combined treatment with ZTR and temozolomide conferred a profound benefit of mPFS over historical control. The study additionally found ZTR to be well tolerated. The trial was sponsored and conducted by the NCI, and NCI expects to publish and report its findings and present them at an upcoming medical conference in 2021.

"Because preclinical data demonstrated the ability of ZTR to inhibit CDK9, enhance apoptosis and cause mitochondrial dysfunction and ultimately ATP depletion in glioma cells, we were optimistic about this first-in-human glioma trial," said Jing Wu, M.D., Ph.D., NCI’s Principal Investigator of the 17-C-0009 trial. "The data from the Phase 1b trial support our initial expectations and reinforce our energies to continue to investigate ZTR as a treatment for patients with gliomas."

"We are very grateful to our NCI colleagues, the patients, and their families for their participation in this trial. Recurrent high-grade gliomas are aggressive malignant brain tumors and remain difficult cancers to treat. Currently, available agents used for the treatment of gliomas offer little or no proven benefit; new therapeutic options are needed," said Scott Megaffin, Chief Executive Officer of Adastra. "We are exceptionally encouraged by the potential of zotiraciclib as a new treatment alternative for patients with recurrent high-grade gliomas. On the basis of these findings, Adastra is in active preparation of a registration-enabling clinical study of ZTR in patients with recurrent high-grade gliomas, in addition to work now underway to expand the application of ZTR to additional solid tumors and hematologic malignancies."

The majority of glioblastoma multiforme (GBM) cases are recurrent, and the mortality rate for patients with recurrent gliomas is nearly 100%, representing a significant unmet medical need. Furthermore, currently approved treatment options for recurrent, high-grade gliomas have limited effectiveness, creating the need for medicines like ZTR, which possesses a unique mechanism of action. ZTR is a potent oral CDK9 inhibitor with the ability to readily cross the blood-brain barrier and deplete short-lived proteins like Mcl-1 and Myc, known antiapoptotic oncogenes.

On January 13, 2021 Philogen S.p.A., a clinical-stage biotechnology company focused on antibody-based therapeutics, reported that 50% of the expected events for the primary outcome analysis of the PIVOTAL study were reached in December 2020 (Press release, Philogen, JAN 13, 2021, View Source [SID1234573982]). In this phase III clinical trial, the effect of Nidlegy is evaluated in melanoma patients with locally advanced, fully resectable metastatic cancer, and at the time of the second interim analysis, had already recruited 149 out of the anticipated 214 patients (one additional patient was enrolled recently). As a consequence, the second interim data analysis foreseen by the clinical protocol was carried out and submitted to the Data and Safety Monitoring Board of the study for their consideration. On Dec. 22, 2020, the DSMB met to review the data and issued to the company a recommendation to continue with the study and patient accrual as detailed by the clinical protocol.

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PIVOTAL is a phase III, international, multi-center, randomized, comparator-controlled, parallel-group study evaluating the efficacy and safety of intratumoral injections of Nidlegy as a neoadjuvant, followed by standard-of-care treatment (surgery + approved adjuvants), as opposed to standard-of-care treatment alone, in melanoma patients with locally advanced, fully resectable cutaneous, sub-cutaneous, or nodal metastases, accessible to intratumoral injection. A first interim analysis at 25% of the expected events and 82 enrolled patients had already been carried out in March 2019.

The primary endpoint of the trial comprises the assessment of Recurrence-Free Survival at one year after randomization. Secondary endpoints include Overall Survival, Local Recurrence-Free Survival and Distant Metastasis-Free Survival, as well as Safety.

The study is expected to include 214 patients across more than 20 centers (currently 18 centers) in four different EU countries (France, Germany, Italy, Poland).

Dario Neri, Chief Executive Officer of Philogen, commented, "We are extremely pleased to record the PIVOTAL study DSMB’s recommendation to carry on with the study as originally planned. This reinforces the confidence in our strategy to bring Nidlegy to the market as a new therapeutic opportunity for melanoma patients."

On January 13, 2021 Inhibrx, Inc. (Inhibrx), a clinical-stage biotechnology company with a broad pipeline of biotherapeutics in development, reported the U.S. Food and Drug Administration (FDA) granted Fast Track designation to INBRX-109 for the treatment of patients with unresectable or metastatic conventional chondrosarcoma (Press release, Inhibrx, JAN 13, 2021, View Source [SID1234573981]). INBRX-109 is a precisely engineered tetravalent single domain antibody (sdAb)-based therapeutic candidate that agonizes death receptor 5 (DR5) to induce tumor selective programmed cell death.

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Fast Track designation is granted by the FDA upon the request of the sponsor to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening diseases. Depending upon the stage of the product’s development, the sponsor must also provide FDA with nonclinical or clinical data to demonstrate the drug’s potential to address unmet medical needs for such a disease or condition. Investigational drug products with Fast Track designation may benefit from early and frequent communication with the FDA, and are eligible for rolling submission and FDA review of its future marketing application. The designation was granted to INBRX-109 based on preliminary data from the chondrosarcoma expansion cohort of the Phase 1 clinical trial of INBRX-109.

"There are currently no approved agents for the treatment of unresectable or metastatic conventional chondrosarcoma, and we are excited about the potential of this treatment to meaningfully improve the outcome for patients," said Mark Lappe, CEO of Inhibrx. "We look forward to working closely with the FDA throughout the clinical development of INBRX-109."

A potential registration-enabling Phase 2 study of INBRX-109 has been discussed with the FDA and will be designed as a randomized, blinded, placebo-controlled study in unresectable or metastatic conventional chondrosarcoma with progression-free survival as the primary endpoint. Inhibrx expects to start dosing patients in this potentially registration-enabling study in the second or third quarter of this year.

About the Inhibrx sdAb Platform

Inhibrx utilizes diverse methods of protein engineering in the construction of therapeutic candidates that can address the specific requirements of complex target and disease biology. A key tool for this effort is the Inhibrx proprietary sdAb platform, which enables the development of therapeutic candidates with attributes superior to other monoclonal antibody and fusion protein approaches. This platform allows the combination of multiple binding units in a single molecule, enabling the creation of therapeutic candidates with defined valency or multiple specificities, potentially capable of enhanced cell signaling or conditional activation. An additional benefit of this platform, these optimized, multi-functional entities can be manufactured using the established processes that are commonly used to produce therapeutic proteins.

Initially, Inhibrx is pursuing targets with early clinical validation, such as DR5, where other therapeutics have demonstrated liabilities. In addition, Inhibrx is developing a portfolio of sdAb based therapeutic candidates in a variety of indications for both known and novel targets.

On January 13, 2021 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, announced that it will report fourth quarter and full year 2020 results on Thursday, February 4, 2021, before the market opens (Press release, Quest Diagnostics, JAN 13, 2021, View Source [SID1234573980]). It will hold its quarterly conference call to discuss the results beginning at 8:30 a.m. Eastern Time on that day.

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The conference call can be accessed by dialing 888-455-0391 within the U.S. and Canada, or 773-756-0467 internationally, using the passcode: "7895081." The earnings release and live webcast will be posted on www.QuestDiagnostics.com/investor. The company suggests participants dial in approximately 10 minutes before the call.

A replay of the call may be accessed online at www.QuestDiagnostics.com/investor or by phone at 866-461-2735 for domestic callers or 203-369-1352 for international callers; no passcode is required. Telephone replays will be available from approximately 10:30 a.m. Eastern Time on February 4, 2021 until midnight Eastern Time on February 18, 2021.

Anyone listening to the call is encouraged to read the company’s periodic reports on file with the Securities and Exchange Commission, including the discussion of risk factors and historical results of operations and financial condition in those reports.

On January 13, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that clinical and preclinical updates at the 39th Annual J.P. Morgan Healthcare Conference (Press release, Precigen, JAN 13, 2021, View Source [SID1234573979]). Helen Sabzevari, PhD, President and CEO of Precigen, presented a summary of 2020 clinical achievements and set forth Precigen’s clinical goals for 2021.

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In addition to reviewing the latest clinical updates for Precigen’s PRGN-3005 UltraCAR-T, PRGN-3006 UltraCAR-T, AG019 ActoBiotics, the presentation included the following additional announcements:

UltraCAR-T Library Approach: Precigen introduced the Company’s vision for a new UltraCAR-T library approach to transform the personalized cell therapy landscape for cancer patients. Precigen’s goal is to develop and validate a library of non-viral plasmids to target tumor-associated antigens. Enabled by design and manufacturing advantages of UltraCAR-T, coupled with the capabilities of the UltraPorator system, Precigen is working to empower cancer centers to deliver personalized, autologous UltraCAR-T treatment with overnight manufacturing to any cancer patient. Based on the patient’s cancer indication and biomarker profile, one or more non-viral plasmids would be selected from the library to build a personalized UltraCAR-T treatment. After initial treatment, this approach has the potential to allow for redosing of UltraCAR-T targeting the same or new tumor-associated antigen(s) based on the treatment response and the changes in antigen expression of the patient’s tumor. Precigen believes that the combination of the advanced UltraVector DNA construction platform and the ease of overnight manufacturing gives this library approach a proprietary advantage over traditional T-cell therapies.
PRGN-2009 AdenoVerse Immunotherapy in HPV-associated Cancers: For the first time, Precigen provided preliminary data for the ongoing Phase I/II study of the first-in-class PRGN-2009 AdenoVerse immunotherapy to treat HPV-positive (HPV+) solid tumors. The Phase I study is evaluating safety and response of PRGN-2009 alone (Arm A) and in combination with bintrafusp alfa, an investigational bifunctional fusion protein, (Arm B) in patients with HPV-associated cancers under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI).
PRGN-2009 differentiation: PRGN-2009 leverages Precigen’s UltraVector and AdenoVerse platforms to optimize HPV 16/18 antigen design for delivery via a proprietary gorilla adenovector with a large genetic payload capacity and the ability for repeat administrations.
Preclinical activity: Preclinical studies show that PRGN-2009 treatment induced a strong HPV-specific immune response and anti-tumor response in a syngeneic mouse model of HPV+ cancer.
Addressable patient population: HPV infections account for 5% of all cancers globally1 and 690,000 new cancer cases are attributable to HPV infections per year.2
Enrollment: Enrollment in the Phase I monotherapy dose escalation arm (Arm A) is complete and enrollment in the Phase I combination arm (Arm B) has initiated.
Clinical activity: All patients (N=6) enrolled in the Phase I monotherapy arm (Arm A) have received multiple PRGN-2009 administrations to date and repeated administration of PRGN-2009 treatment has been well-tolerated with no dose-limiting toxicities.
Preliminary correlative analysis of peripheral blood mononuclear cells (PBMC) from patients treated at Dose Level 1 demonstrated an increase in HPV 16 and/or HPV 18-specific T-cell response post PRGN-2009 administration in 100% (3 out of 3) of patients; and
An increase in magnitude and breadth of immune response has been shown with respect to repeat administration of PRGN-2009.
Preclinical data for two new AdenoVerse immunotherapies:
PRGN-2012 AdenoVerse Immunotherapy in Recurrent Respiratory Papillomatosis (RRP): Precigen presented data from preclinical studies in which PRGN-2012 was shown to induce robust HPV 6 and HPV 11-specific T-cell response in RRP patient samples in vitro. Precigen recently announced that the US Food and Drug Administration (FDA) cleared the Investigational New Drug (IND) application to initiate the Phase I clinical trial of PRGN-2012 AdenoVerse immunotherapy in adult patients with recurrent respiratory papillomatosis (RRP).
PRGN-2013 AdenoVerse Immunotherapy in Hepatitis B Virus (HBV) Infection: Precigen shared preclinical data for PRGN-2013, which incorporates novel HBV antigen design in a proprietary gorilla adenovector, which showed that PRGN-2013 induces superior cytotoxic T-cell response against more HBV epitopes in mice than a competitor vaccine candidate and decreases plasma levels of HBsAg, the key marker of chronic HBV infection.
"In spite of the challenges presented by the COVID-19 pandemic, Precigen has accomplished all of the clinical milestones we set for ourselves in 2020," said Helen Sabzevari, PhD, President and CEO of Precigen, "I am proud of the team and collaborators for their commitment and execution during this challenging time which made possible the continued advancement of our differentiated therapeutics aimed at benefiting patients with severe unmet needs."

Precigen’s J.P. Morgan presentation is available on the Company website in the Events & Presentations section at investors.precigen.com/events-presentations.