On June 9, 2021 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), hereafter "Onxeo" or "the Company", a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR), in particular against rare or resistant cancers, reported that it has received from the U.S. Patent and Trademark Office (USPTO), a Notice Allowance for a patent which enhances in the United States the protection of AsiDNA, its first- in-class inhibitor of tumor DNA repair, in combination with any PARP inhibitor (PARPi) (Press release, Onxeo, JUN 9, 2021, View Source [SID1234583763]). This patent protects both the combination of AsiDNA with a PARPi and its use for the treatment of certain cancers for which the DNA repair pathway via homologous recombination (HR) is not impaired or deficient. These so-called HR-proficient tumors are significantly less sensitive to treatment with PARP inhibitors.

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!

This new patent completes, in a key territory, the already robust patent family protecting AsiDNA in combination with PARP inhibitors. It will provide a term of protection until 2036.

The DNA repair pathways, BRCA-dependent homologous recombination pathway and PARP pathway, are complementary and essential for tumor cell survival and proliferation. If one pathway is deficient (homologous recombination by BRCA mutation) and the other is blocked by a PARP inhibitor, the tumor cell dies. This deadly combination of two genetic mutations, called synthetic lethality, is a prerequisite to PARPi efficacy.

This patent is based on the fact that AsiDNA is able, through its original mechanism of action, to hinder DNA repair pathways, including the homologous recombination pathway. AsiDNA thus induces a context of "HR deficiency" needed by PARPi to be effective, regardless of the initial genetic context of the tumor.

"This patent represents a further recognition in the strategic US market of the very original properties of AsiDNA. We have already started the clinical demonstration that AsiDNA has the potential to reverse the resistance acquired to a PARP inhibitor, notably thanks to its effect on the drug-tolerant cells who play a key role on acquired resistance. The drug-induced synthetic lethality provided by AsiDNA opens an important new application to our lead product. Indeed, extending the efficacy of PARP inhibitors to the important group of HR-proficient patients could represent another major therapeutic opportunity," said Judith Greciet, Chief Executive Officer of Onxeo.

PARPi have demonstrated a real clinical benefit[1], particularly in the treatment of ovarian cancer with BRCA mutations, but this benefit is much reduced, or even insignificant, when homologous recombination remains active, which is the case in about 50% of patients[2].

[1] Moore et al. N Engl J Med 2018; 379:2495-2505

[2] Zeimet, A.G., Wieser, V., Knoll, K. et al. PARP inhibitors in the treatment of ovarian cancer. memo (Magazine of European Medical Oncology) 13, 198–201 (2020).

On June 9, 2021 NanOlogy, LLC, a clinical-stage oncology company, reported that additional data from its Phase 2 dose-rising and expansion clinical trial of intracystic NanoPac for mucinous cystic neoplasms of the pancreas were presented via poster by Somashekar Krishna, MD, MPH of The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center during Digestive Disease Week held virtually from May 21-23, 2021 (Press release, NanOlogy, JUN 9, 2021, View Source [SID1234583762]). NanoPac is composed of large surface area microparticles of pure paclitaxel designed as a drug depot for local administration and sustained drug release over several weeks. In this study, the investigational drug was delivered once or twice via endoscopic ultrasound guided fine needle injection following aspiration of cyst fluid in patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) or mucinous cystic neoplasms (MCNs).

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 6-month trial enrolled 19 subjects and was completed in late 2020. The clinical study report was submitted to FDA in April 2021 and clinical trial results can be found at NCT03188991 in clinicaltrials.gov. Overall, the drug was well tolerated with no dose limiting toxicities or drug-related significant adverse events observed. Reduction in cyst volume was demonstrated in 14/19 (74%) of subjects at 6 months.

Dr. Krishna presented a series of five subjects enrolled at his clinical site in whom additional testing revealed no detectable DNA mutations in 2/4 subjects following NanoPac treatment, all of whom were positive at baseline. Absence of DNA indicates the possibility of cyst epithelial lining necrosis, a key goal in treatment. In addition, high concentrations of paclitaxel (>1000 ng/mL) were found in cyst fluid prior to the second injection at the 3-month timepoint confirming retention of NanoPac in the cyst while plasma concentrations were never greater than 3.5 ng/mL at any timepoint.

Large IPMNs or MCNs grow rapidly and are at high risk for progression to pancreatic cancer, one of the deadliest of all cancers. Surgery is recommended to eliminate the risk, but a significant number of patients refuse or cannot withstand surgery due to the associated morbidities. For these patients, there are few therapeutic options and no approved drug therapies. Additional studies of NanoPac are being considered to further evaluate its potential in these patients.

In addition to this trial, NanOlogy’s clinical programs are advancing in pancreatic, lung, genitourinary, and dermal cancers. Data from preclinical and clinical studies in a variety of solid tumors indicate persistent tumor kill, antitumoral immune response, and minimal local or systemic toxicity.

The NanOlogy large surface area microparticle (LSAM) therapeutic platform is based on a proprietary supercritical precipitation technology that converts taxane API crystals into stable LSAMs of pure drug for tumor-directed therapy and sustained drug release. The taxane particles are covered by composition of matter patents issued in the US (US 9,814,685, US 10,507,195, & US 10,993,927), Europe, Japan, and Australia all valid until 2036, plus applications pending globally. These composition of matter patents form the foundation of an extensive intellectual property portfolio protecting the investigational drugs, methods, and technology.

On June 9, 2021 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer, reported the Russell Microcap Index at the conclusion of the 2021 Russell indexes annual reconstitution effective after the US market opens on June 28, according to a preliminary list of additions posted June 4 (Press release, Panbela Therapeutics, JUN 9, 2021, View Source [SID1234583761]).

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!

Membership in the Russell Microcap Index, which remains in place for one year, means automatic inclusion in the appropriate growth and value style indexes. FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes.

"We look forward to the opportunity to communicate our strategy and accomplishments with a broader investor audience that inclusion in the Microcap Index will provide," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer. "We are moving our research programs forward and believe the progress we are making will provide a compelling investment opportunity."

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $10.6 trillion in assets are benchmarked against Russell’s US indexes. Russell indexes are part of FTSE Russell, a leading global index provider.

For more information on the Russell Microcap Index and the Russell indexes reconstitution, go to the "Russell Reconstitution" section on the FTSE Russell website www.ftserussell.com.

About SBP-101

SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, suggesting potential complementary activity with an existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Recently observed serious visual adverse events are being evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial generally provides potential support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source

On June 9, 2021 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") reported that preliminary mycosis fungoides data from the Phase 2 TELLOMAK trial evaluating lacutamab, an anti-KIR3DL2 cytotoxicity-inducing antibody in development for T-cell lymphomas, will be presented during an oral presentation at the virtual 16th International Conference on Malignant Lymphoma (16-ICML) taking place from June 18-22, 2021 (Press release, Innate Pharma, JUN 9, 2021, View Source [SID1234583753]).

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!

Oral presentation details:

Title: Lacutamab in patients with advanced mycosis fungoides according to KIR3DL2 expression: early results from the TELLOMAK phase 2 trial

Date and time: June 22, 2021 at 1 p.m. CEST

Abstract number: 054

TELLOMAK trial investigator, Martine Bagot, M.D., Ph.D., Professor of Dermatology, Head of the Dermatology Department at the Saint-Louis Hospital, University of Paris, will deliver the oral presentation.

Pr. Bagot will also present the data during an Innate Pharma online webcast for the financial community on June 23, 2021. Details about this webcast will be provided on the Company website by June 16, 2021.

About Lacutamab:

Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, which is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral t-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

About TELLOMAK:

TELLOMAK is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with advanced T-cell lymphomas (TCL) in the United States and Europe. TELLOMAK is expected to recruit up to 150 patients, with lacutamab evaluated:

As a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab.
As a single agent in approximately 90 patients with mycosis fungoides (MF) who have received at least two systemic therapies.
In patients with MF, the study is designed to evaluate the effect of lacutamab according to KIR3DL2 expression. The study comprises two cohorts in MF, testing lacutamab in KIR3DL2 expressing and non-expressing patients determined at baseline. These cohorts follow a Simon 2-stage design that will terminate early if treatment is considered futile. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.

The primary endpoint of the trial is objective response rate. Key secondary endpoints are progression-free survival, duration of response, quality of life and adverse events.

On June 9, 2021 eFFECTOR Therapeutics, Inc., a leader in the development of selective translation regulation inhibitors (STRIs) for the treatment of cancer, reported that the first patient with non-small cell lung cancer (NSCLC) has been dosed in a Phase 2b trial of tomivosertib in combination with KEYTRUDA (pembrolizumab) (Press release, eFFECTOR Therapeutics, JUN 9, 2021, View Source [SID1234583750]). KICKSTART is a randomized, double-blind, placebo-controlled clinical trial assessing the efficacy and safety of tomivosertib in combination with pembrolizumab, a U.S. Food and Drug Administration (FDA)-approved PD-1 inhibitor, as frontline combination therapy or as an extension of frontline therapy at the first radiographic progression of disease on pembrolizumab therapy alone. Patients enrolled in this trial will have demonstrated biomarker expression of PD-L1 >50% assessed by an FDA-approved diagnostic test. These NSCLC patients are generally the most responsive patient population to immunotherapy and for whom treatment with checkpoint inhibitors as a monotherapy is the standard of care.

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!

"We observed in our Phase 2a trial of tomivosertib in combination with checkpoint inhibitors that following disease progression, the addition of tomivosertib was correlated with a noted change in tumor trajectory, as well as durable treatment benefit, demonstrating our product candidate’s potential to reverse resistance to checkpoint inhibitors. Furthermore, a retrospective analysis of the Phase 2a data showed that PD-L1 positivity correlated with duration of benefit, supporting use of PD-L1 >50% as a biomarker for patient selection in KICKSTART," said Steve Worland, Ph.D., president and CEO of eFFECTOR. "Based on those encouraging results that substantially extended patient benefit from immunotherapy, we are launching KICKSTART to be focused in both the frontline and frontline-extension settings in combination with pembrolizumab. We designed tomivosertib to down-regulate multiple factors that suppress an immune response and to reprogram T cells to enhance immune response and fight tumors, and ultimately hope to bring a novel and improved treatment option for patients with cancer."

The KICKSTART trial is designed to enroll approximately 120 participants in two cohorts. Cohort one is a frontline-extension cohort that will assess the efficacy and safety of adding tomivosertib to the treatment regimen in combination with pembrolizumab for patients who initially benefited from therapy and then developed radiographic progression on treatment with pembrolizumab alone. Cohort two will assess the safety and efficacy of tomivosertib in combination with pembrolizumab at treatment initiation in the frontline setting. Both cohorts in the trial will have a control arm with placebo in combination with pembrolizumab. The primary endpoint of the trial is progression free survival (PFS) in each the frontline-extension and frontline settings. In addition, PFS in the combined population from both cohorts, overall survival (OS) and overall response rate (ORR) will be assessed as secondary endpoints. Additional information about the trial can be found at www.clinicaltrials.gov under the identifier NCT04622007.

About Tomivosertib (eFT508)
Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2). The oral, small molecule drug candidate has been shown to enhance killing of tumor cells by T cells, delay T-cell exhaustion/dysfunction and enhance the T-cell central memory pool, in part by down-regulating multiple checkpoint proteins including PD-1, PD-L1, TIM-3 and LAG-3. Tomivosertib is being evaluated in KICKSTART, eFFECTOR’s randomized, double-blind, placebo-controlled Phase 2b study in NSCLC in combination with pembrolizumab. The KICKSTART trial builds on results obtained in an earlier study of tomivosertib as an extension of checkpoint inhibitor treatment in patients experiencing insufficient response to an FDA-approved checkpoint inhibitor alone.

Please visit www.clinicaltrials.gov for further information on ongoing clinical trials of tomivosertib.