On November 12, 2021 Neoleukin Therapeutics, Inc., "Neoleukin" (NASDAQ:NLTX), a biopharmaceutical company utilizing sophisticated computational methods to design de novo protein therapeutics, reported the presentation of new preclinical data on NL-201, an alpha-independent, de novo-designed IL-2 and IL-15 dual agonist, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 36TH Annual Meeting (SITC 2021) (Press release, Neoleukin Therapeutics, NOV 12, 2021, View Source [SID1234595447]).

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The presentation highlights preclinical data on NL-201 alone and in several combination regimens. NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the IL-2 receptor alpha subunit (CD25).

"The SITC (Free SITC Whitepaper) presentations highlight the broad potential of NL-201, which we believe to be the first fully de novo designed protein to enter clinical trials, to activate the immune system to fight cancer," said Jonathan Drachman, M.D., Chief Executive Officer of Neoleukin. "New data demonstrate that NL-201 can activate the tumor microenvironment and increase T-cell receptor diversity. We also found that local, intratumoral administration can control both the injected and distant tumors with improved tolerability compared to systemic administration in pre-clinical models. We are pleased to share this research as we continue to advance the NL-201 phase 1 clinical trial."

Further details from the presentations are as follows:

Poster/Abstract Number: 716
NL-201 Induces Inflammation in a ‘Cold’ Tumor Microenvironment through Upregulation of MHC-I, Expansion of the TCR Repertoire, and Potent Antitumor Activity when Combined with PD-1 Inhibition

NL-201 turns "cold" tumors "hot" by increasing pro-inflammatory T cells and an immune signature in the tumor microenvironment and upregulating MHC-1 in tumors.
NL-201 stimulates pro-inflammatory tumor reprogramming without the coincident Treg expansion observed with PD-1 antibodies and other immuno-oncology agents.
NL-201 drives anti-tumor efficacy in a manner that is cooperative with PD-1 inhibition, including increasing TCR repertoire diversity.
Poster/Abstract Number: 898
Intratumoral Administration of NL-201, an Alpha-Independent IL-2/15 Receptor Agonist, Inhibits the Growth of Both Injected and Uninjected Tumors in Preclinical Models

Intratumoral NL-201 administration demonstrated:
Dose-dependent antitumor activity in syngeneic murine tumor models;_
Improved tolerability compared to systemic administration at equivalent dose levels and;
Durable tumor-specific immunity.
Results support clinical investigation of intratumoral NL-201 administration to increase NL-201 concentration in accessible lesions and reduce systemic exposure.
Poster/Abstract Number: 509
A First-in-Human Phase 1 Study of NL-201 in Patients with Relapsed or Refractory Cancer (Trials in Progress)

Assessing the safety profile and recommended Phase 2 dose and treatment schedule of NL-201.
Dose escalation and dose expansion cohorts.
Enrollment ongoing at multiple sites in North America and Australia.
Poster/Abstract Number: 563
ICT01, an Anti-BTN3A Monoclonal Antibody, and NL-201, an Alpha-Independent IL-2/IL-15 Agonist, Combine to Elicit a Potent Anti-Tumor Response by Synergistically Stimulating g9d2 T Cell Activation and Proliferation

ICT01 plus NL-201 synergistically triggers gd T-cell activation, expansion and antitumor activity.
Data support clinical evaluation of this novel therapeutic approach.
The poster presentations are available on the Neoleukin website publications page: View Source

About NL-201
NL-201 is a de novo agonist of the IL-2 and IL-15 receptors, designed to expand cancer-fighting CD8 T cells and natural killer (NK) cells without any bias toward cells expressing the alpha receptor subunit (CD25). Previously presented preclinical data has demonstrated the ability of NL-201 to stimulate and expand CD8+ and NK cells at low doses with minimal impact on immunosuppressive regulatory T cells. Furthermore, NL-201 has demonstrated both monotherapy and combination activity across a wide range of preclinical syngeneic tumor models.

On November 12, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported the Company’s CEO Dr. Pnina Fishman will present at the H.C. Wainwright 7th Annual Israel Conference on Monday, November 15, 2021 at 12:30 PM ET (Press release, Can-Fite BioPharma, NOV 12, 2021, View Source [SID1234595446]). In addition to the presentation, management will conduct one-on-one meetings with investors at the virtual conference.

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Dr. Fishman will highlight Can-Fite’s advanced stage pipeline including a completed Phase III study in psoriasis with data anticipated in Q1 2022 and upcoming studies that are expected to commence enrollment including a Phase II study in NASH and a pivotal Phase III in liver cancer.

On November 12, 2021 Checkmate Pharmaceuticals, Inc. (NASDAQ: CMPI) ("Checkmate"), a clinical stage biotechnology company focused on developing proprietary technology to harness the power of the immune system to combat cancer, reported the presentation of final clinical data from the Phase 1b study, CMP-001-001 (NCT02680184), of vidutolimod, an advanced generation Toll-like receptor 9 (TLR9) agonist, in combination with pembrolizumab or as a monotherapy at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting taking place on November 10-14, 2021 (Press release, Checkmate Pharmaceuticals, NOV 12, 2021, View Source [SID1234595445]).

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"Our ongoing investigation of vidutolimod indicates promising clinical activity for patients with PD-1 blockade-refractory melanoma," said Alan Fuhrman, interim President and Chief Executive Officer of Checkmate. Mr. Fuhrman added, "The RECIST response rates of 20% with vidutolimod monotherapy and 23.5% in combination with pembrolizumab are compelling, and the longer duration of response of 25.2 months in combination with PD-1 blockade provides a strong rationale for our ongoing development program."

Final analysis: phase 1b study investigating intratumoral injection of Toll-like receptor 9 agonist vidutolimod ± pembrolizumab in patients with PD-1 blockade–refractory melanoma (Abstract #16269; poster #950; NCT02680184)

On Friday, November 12, 2021, during the Virtual Poster Hall Exhibit from 7:00am – 8:30pm ET, John M. Kirkwood, M.D., Director of the Melanoma and Skin Center at UPMC Hillman Cancer Center and Usher Professor of Medicine in the Division of Dermatology and Translational Science at the University of Pittsburgh School of Medicine, is presenting late-breaking final clinical data from the Checkmate-sponsored clinical trial of vidutolimod, either in combination with pembrolizumab or as monotherapy.

Final clinical data from the trial demonstrated that the combination of vidutolimod and pembrolizumab was well tolerated and resulted in an ORR of 23.5% according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The study treatment induced deep and durable systemic antitumor responses in patients with melanoma who previously progressed on anti-PD-1 treatments.

"PD-1 blockade therapy has significantly improved clinical outcomes for many patients with cancer, although most patients still experience disease progression on anti−PD-1-therapy. Therapeutic alternatives for these patients are a large gap in the field, and critically needed," said Dr. Kirkwood. "With clinically meaningful tumor regression we have observed both in injected and noninjected lesions, vidutolimod’s systemic effects hold the potential to enhance responsiveness and overcome resistance to immune checkpoint inhibitors. In addition, the substantially improved duration of response with the combination of vidutolimod and anti-PD-1 therapy provides strong rationale for further development of vidutolimod in combination with PD-1 blockade."

Data were presented on 159 patients receiving combination therapy with vidutolimod and pembrolizumab. Two formulations of vidutolimod were evaluated, either polysorbate 20 at 0.01% (PS20, n=98) or x PS20 at 0.00167% (n=61). Based on the results, vidutolimod PS20 A 10 mg (schedule A) was selected as the Recommended Phase 2 Dose (RP2D) and schedule. Data were also presented on 40 patients who received vidutolimod monotherapy.

Key highlights from these clinical data as of the data cut-off of August 17, 2021 include:

Vidutolimod in combination with pembrolizumab

The best ORR by RECIST v1.1 in patients who received vidutolimod PS20 A+ pembrolizumab was 23.5% (95% CI 15.5-33.1), including 7.1% (7/98) of patients with a complete response.
Four additional patients who continued study therapy beyond initial disease progression achieved a partial response.
Vidutolimod PS20 A 10 mg (schedule A) was selected as the RP2D.
The Kaplan-Meier estimate for median duration of response was 25.2 months (95% CI8.7- not estimable [NE] in the 23 RECIST v1.1 responders).
Among responding patients, non-injected target lesions regressed by a similar magnitude to injected target lesions.
The most common treatment-related adverse events were chills, pyrexia, fatigue, nausea, vomiting and injection site pain.
Vidutolimod as a monotherapy

In the 40 patients who received vidutolimod monotherapy, the best ORR by RECIST v1.1 was 20.0% (95% CI, 9.1-35.6).
The median duration of response was 5.6 months (95% CI, 3.1-NE).
The most common treatment-related adverse events were chills, pyrexia, nausea, fatigue, headache, hypotension, and pruritus.

On November 12, 2021 Ocuphire Pharma, Inc. (Nasdaq: OCUP), a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of refractive and retinal eye disorders, reported financial results for the third quarter of 2021 and provided a corporate update (Press release, Ocuphire Pharma, NOV 12, 2021, View Source [SID1234595444]).

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"The third quarter marked continued progress across our late-stage clinical programs and opportunities for multiple data presentations at major medical meetings," said Mina Sooch, MBA, President and CEO of Ocuphire Pharma. "We have already achieved two successful clinical trials for Nyxol. In reversal of mydriasis (RM), we reported positive results in a Phase 3 trial and are on track to initiate the second Phase 3 trial before year end. In presbyopia, we reported positive results in a Phase 2 clinical trial. We are also delighted to see the early US regulatory approval of Allergan’s VUITYTM eye drops, the first pharmaceutical therapy for the large presbyopia market."

"We are also very pleased to see a growing body of supportive research for our Phase 2 oral drug candidate, APX3330, which inhibits known pro-angiogenic and pro-inflammatory pathways. As a highly differentiated, first-in-class and orally-delivered therapy, we believe APX3330 will be an important source of potential value creation with the opportunity to broadly address the unmet global clinical need in diabetic retinopathy and treatment burden in other retinal diseases."

"This week marks Ocuphire’s one-year anniversary of public trading on the Nasdaq and we are proud to have achieved so many important clinical and business milestones in that time. We thank our clinical trial participants and investigators for their continued support. Looking ahead, we believe 2022 is shaping up to be an even more exciting and catalyst-rich year to build significant value for our company and our shareholders, with cash on hand that provides runway into late 2022 to achieve these milestones."

Key Anticipated Future Milestones

Reversal of Mydriasis (RM): Initiate second Phase 3 (MIRA-3) registration trial in subjects 12 and older and a small pediatric trial in subjects ages 3 to 11 (MIRA-4) in the fourth quarter of 2021 investigating Nyxol with results expected in early 2022; Planning to file NDA submission with FDA for Nyxol in RM indication in late 2022
Presbyopia: Initiate Phase 3 program (VEGA-2) in first half of 2022 investigating Nyxol and Low-Dose Pilocarpine (LDP)
Night Vision Disturbances (NVD): Top-line data expected in early 2022 from Phase 3 (LYNX-1) registration trial investigating Nyxol
Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME): Top-line data expected in the second half of 2022 for the randomized, well-controlled Phase 2 (ZETA-1) trial investigating APX3330
Third Quarter and Recent Business Highlights

Presentations and Publications

In November, clinical data on Nyxol and APX3330 were accepted for presentation at poster sessions at the American Academy of Ophthalmology (AAO) 2021 annual meeting to take place in New Orleans, November 12 – 15. In addition, Ocuphire presented new data on improvement in intermediate vision and Snellen equivalent near vision at the [email protected] 2021 conference on November 11. Ocuphire was one of two companies presenting clinical data for presbyopia at this meeting.
In October, the Company announced the publication of a review article within the Special Issue "Advances in Molecular Activity of Potential Drugs" of the International Journal of Molecular Sciences, focused on how novel inhibitors of APE1/Ref-1 such as APX3330 may have the potential to improve disease outcomes for retinal disease patients. The article underscores the role of the APE1/Ref-1 protein in pro-angiogenic pathways associated with neovascular eye disease including diabetic retinal diseases and age-related macular degeneration. It can be accessed online at the following link: Inhibition of APE1/Ref-1 for Neovascular Eye Disease: From Biology to Therapy.
In October, the Company announced the publication of a review article in Cells titled "Potential Therapeutic Candidates for Age-Related Macular Degeneration" noting the potential of APX3330 (referred to as "E3330") for the treatment of age-related macular degeneration (AMD). Because APE1/Ref-1 has been shown to contribute to retinal angiogenesis, the authors conclude that APE1/Ref-1 inhibitors such as APX3330 could inhibit the abnormal blood vessel formation seen in AMD by reducing retinal endothelial cell proliferation, migration, and tube formation. The article can be accessed online at the following link: Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD).
In October, Michael J. Allingham, MD, PhD presented at the 39th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) (Diabetic Retinopathy 1 Symposium), highlighting the favorable safety and tolerability data for APX3330 in over 300 healthy volunteers and cancer/inflammation disease patients across 11 Phase 1 and Phase 2 studies. Also, Mina Sooch, CEO, presented APX3330 history and the design of the ongoing Phase 2 trial in DR at the OIS Retina Innovation [email protected].
In July, the Company announced publication in the Journal of Cellular Signaling featuring Ocuphire’s novel oral Ref-1 inhibitor APX3330 in Phase 2 trial for the treatment of retinal disease which highlighted the favorable safety profile of APX3330 and its unique anti-angiogenic and anti-inflammatory mechanism of action properties relevant to a broad range of retinal diseases.
In July, at the 2021 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting, Dr. Jay S. Pepose, Medical Advisor and Board Director, presented papers featuring positive results for Nyxol in two studies: Phase 2 Presbyopia (VEGA-1) and Phase 3 Reversal of Mydriasis (MIRA-2). The Phase 3 MIRA-2 data presentation at ASCRS won the Best Paper of the Session.
In July, Mina Sooch, CEO, participated in the presbyopia drug therapy panel at the [email protected] 2021 held on July 22nd and in the Eye on Innovation panel at the Virtual Salon Series held on July 28th.
Intellectual Property

U.S. Patent and Trademark Office issued patent no. 11,160,770 "Compounds, compositions and methods for treating oxidative DNA damage disorders" which provides protection for APX2009 and other APX pipeline candidates.
Third Quarter and Year-To-Date 2021 Financial Highlights

As of September 30, 2021, the Company had cash and cash equivalents of approximately $22.2 million. Net cash used in operating activities for the nine months ended September 30, 2021 was $13.7 million.

Collaborations revenue was $0.5 million and $0.6 million for the three months and nine months ended September 30, 2021, respectively. Revenue during the periods was derived from the license agreements with Biosense Global, LLC and Processa Pharmaceuticals, Inc. related to certain technology transfers. There was no collaborations revenue recognized during the comparable prior year periods.

General and administrative expenses for the three months and nine months ended September 30, 2021 were $1.6 million and $6.7 million, respectively, compared to $0.6 million and $1.5 million for the comparable periods in 2020, respectively. The increases in the current periods were primarily attributable to administrative employee headcount, stock-based compensation, professional services, insurance, legal and settlement costs, and costs associated with operating as a public company subsequent to the reverse merger.

Research and development expenses for the three months and nine months ended September 30, 2021 were $3.1 million and $10.4 million, respectively, compared to $1.4 million and $2.3 million for the comparable periods in 2020, respectively. In the current periods, the increases were primarily attributable to new clinical trials and manufacturing activities for Nyxol and APX3330 as well as regulatory, preclinical and other development activities.

The loss from operations for the three and nine months ended September 30, 2021 was $4.2 million and $16.6 million, respectively, compared to $1.9 million and $5.9 million for the three and nine months ended September 30, 2020, respectively.

There was a non-cash expense of $33.8 million related to fair value change in warrant liabilities recorded for the nine months ended September 30, 2021 compared to a benefit of $0.2 million recorded for the nine months ended September 30, 2020 related to premium conversion derivatives. The reported losses also included non-cash stock-based compensation expense of $0.5 million and $1.4 million during the three and nine months ended September 30, 2021, respectively, and $0.6 million and $1.0 million during the three and nine months ended September 30, 2020, respectively.

For further details on Ocuphire’s financial results refer to the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2021, as filed with the Securities and Exchange Commission.

On November 12, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported a poster with preclinical data on its TriTAC-XR T cell engager platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in Washington, D.C (Press release, Harpoon Therapeutics, NOV 12, 2021, View Source [SID1234595443]).

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The poster, titled "TriTAC-XR is an extended-release T cell engager platform designed to minimize cytokine release syndrome (CRS) by reducing Cmax in systemic circulation," showcased preclinical data supporting the novel platform. The platform is designed to minimize on-target cytokine release syndrome, a hallmark of many T cell engagers that can lead to dose limiting toxicities.

Studies in non-human primates with FLT3-targeting T cell engagers confirmed that the slow build-up of active drug and the reduction of differences in peak-to-trough drug concentrations can reduce CRS and improve the safety of T cell engagers. Importantly, the reduction of cytokine release could be achieved while maintaining efficacy in in vivo models. When compared to a TriTAC with the same three binding domains, the TriTAC-XR was able to deplete FLT3-expressing cells with comparable potency despite a 100x reduction in cytokines in cynomolgus monkeys.

"These encouraging data demonstrate that our TriTAC-XR T cell engager platform has the potential to meaningfully mitigate CRS, and we intend to explore if this approach enables the use of T cell engagers for the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies," said Holger Wesche, Ph.D., Chief Scientific Officer of Harpoon Therapeutics.

"The introduction of TriTAC-XR represents the third T cell engager platform and the second protease-activated T cell engager prodrug platform from Harpoon. This further showcases the productivity and creativity of our research efforts, and our commitment to the development of best-in-class T cell engagers," said Julie Eastland, Chief Executive Officer of Harpoon Therapeutics.

Harpoon’s first platform, the constitutively active TriTAC, is designed to minimize off-target toxicities, and is ideal for targets with limited on-target liabilities. The ProTriTAC platform offers similar advantages with activation directed primarily to the tumor microenvironment. This spatial control of activation may address on-target tissue damage, hence enabling an expansion of the T cell engager target space. The TriTAC-XR now adds improved temporal control and is designed to be activated in the systemic circulation at a predefined rate to minimize on-target CRS.

Preclinical data from the TriTAC platform demonstrated:

TriTAC-XR is an extended-release T cell engager platform designed to mitigate cytokine release syndrome by releasing active T cell engagers from an inactive prodrug in a temporally controlled fashion, thus avoiding the very high exposures (Cmax) that occur shortly after administration with constitutively active molecules.
A single dose of FLT3 TriTAC-XR produced similar PD effects with significantly lower cytokines than a comparable TriTAC in non-human primate animal models.
The expected safety improvement of TriTAC-XR could enable the treatment of non-oncology diseases in addition to solid tumors and hematologic malignancies.