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4D pharma presents two clinical posters for MRx0518 at the ESMO Congress 2021

On September 15, 2021 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported that new biomarker analyses from two ongoing clinical trials of its lead immuno-oncology single strain Live Biotherapeutic, MRx0518, in both neoadjuvant and refractory solid tumor settings, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, September 16-21, 2021 (Press release, 4d Pharma, SEP 15, 2021, View Source [SID1234587722]).

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"At the core of 4D pharma’s platform is the importance of understanding the impact of Live Biotherapeutics on human biology to rationally select and develop candidates, predict and measure response. These new biomarker data provide us with critical guidance on the biological and mechanistic impact of MRx0518 therapy in patients with various solid tumors," said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. "These new findings indicate the potential to predict patients most likely to respond to MRx0518 therapy based on tumor biology."

"Furthermore, the monotherapy data demonstrates that a short course of MRx0518 treatment is able to positively modulate prognostic indicators of immunotherapy response," he added. "We look forward to utilizing and implementing these important new findings as we work to progress this novel oncology Live Biotherapeutic through development towards approval."

Highlights of the two ESMO (Free ESMO Whitepaper) 2021 poster presentations:

Baseline biomarkers associated with clinical benefit in patients with solid tumors refractory to immune checkpoint inhibitors (ICIs) treated with live biotherapeutic MRx0518 in combination with pembrolizumab

Presentation Number: 1024P

Tumor biomarkers were assessed in patients with evaluable baseline samples (N = 12) in the ongoing Phase I/II study of MRx0518 in combination with anti-PD-1 immune checkpoint inhibitor (ICI) Keytruda (pembrolizumab)
At baseline, patients who achieved complete response, partial response or stable disease for at least six months (collectively ‘responders’, N=4) from the combination of MRx0518 with Keytruda (pembrolizumab) had significantly greater densities of CD3+FOXP3+CD8- regulatory T cells (Tregs) and CD3+KI67+ proliferating T cells in tumors at baseline, compared to patients with progressive disease (PD, N=8), p=0.0381 and p=0.0048, respectively.
In addition, significantly lower densities of CD68+ macrophages at baseline were observed in the tumor microenvironment of responders compared to patients with progressive disease, p=0.0303.
These data indicate the potential for MRx0518 to overcome Treg-mediated acquired resistance to cancer treatment, and presents a biomarker potentially able to identify patients most likely to respond to immunotherapy based on MRx0518. Further tumor sample analysis is ongoing for additional patients recruited into the study.

Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours

Presentation Number: 543P

Gene expression profiling of paired tumor samples pre- and post-MRx0518 monotherapy across multiple solid tumor types (N=15) showed that treatment with MRx0518 for two to four weeks was associated with anti-tumor immune activity including antigen presentation, innate immune processes, and interferon response.
Analysis of paired tumor samples also identified significant increases in mast cells, Th1, CD8+ T cell, neutrophil, endothelial cell and inflammatory chemokine metagene signatures following MRx0518 monotherapy.
Effects were particularly pronounced in the cohort of breast cancer patients (N=7), with significant increases observed in total and activated dendritic cells, CD8+ T cells and cytotoxic cells in the tumor micro-environment.
Functional metagene analysis also identified positive changes in prognostic indicators and metagene signatures predictive of immunotherapy response in patients with breast cancer, including inflammatory chemokines, cytotoxicity, lymphoid scores, and the Tumor Inflammation Signature (TIS)1 – demonstrated to retrospectively predict clinical benefit of anti-PD-(L)1 ICI therapy efficacy in various cancer types.
The immune biomarker data from this study of MRx0518, as a monotherapy dosed over a short period of just two to four weeks, demonstrates the potent activity of this oral Live Biotherapeutic directly on the human immune system, and the positive implications for clinical outcomes. This study is being conducted in collaboration with Imperial College London.

Both ePosters will be available under the "Posters and Publications" section of the 4D pharma website at www.4dpharmaplc.com at 7:30 GMT on Thursday 16th September 2021.

1 Ayers M, et al. J Clin Invest. 2017;127:2930–40

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumours. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumours and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer. A fourth clinical trial, in collaboration with Merck KGaA and Pfizer Inc., of BAVENCIO (avelumab) in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy, is expected to commence in Q4 2021.

Innate Pharma reports first half 2021 financial results and business update

On September 15, 2021 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported its consolidated financial results for the six months ended June 30, 2021 (Press release, Innate Pharma, SEP 15, 2021, View Source [SID1234587721]). The consolidated financial statements are attached to this press release.

"In the first half of 2021, we had two key advancements in our portfolio – encouraging new lacutamab data in a subtype of cutaneous T-cell lymphoma, mycosis fungoides, and new data from our proprietary, multi-specific NK cell engager platform, ANKET. These progressions have set the stage for delivering both near and long-term value, while also highlighting the strength and depth of our core R&D efforts," said Mondher Mahjoubi, Chief Executive Officer of Innate Pharma. "We look forward to the continued progress of our pipeline, including the upcoming monalizumab presentation at ESMO (Free ESMO Whitepaper) and our lacutamab clinical trial program, in addition to advancing our early-stage R&D activities. These important efforts will help to progress the next wave of innovation at Innate."

Upon registration, participants will be provided with dial-in numbers, a direct event passcode and
a unique registrant ID that they may use 10 minutes prior to the event start to access the call.

This information can also be found on the Investors section of the Innate Pharma website, www.innate-pharma.com.
A replay of the webcast will be available on the Company website for 90 days following the event.
Financial highlights for the first half of 2021:

The key elements of Innate’s financial position and financial results as of and for the six-month period ended June 30, 2021 are as follows:

Cash, cash equivalents, short-term investments and financial assets amounting to €159.4 million (€m) as of June 30, 2021 (€190.6m as of December 31, 2020).
Revenue and other income amounted to €15.7m in the first half of 2021 (€36.7m in the first half of 2020) and mainly comprise of:
Revenue from collaboration and licensing agreements, which mainly resulted from the partial or entire recognition of the proceeds received pursuant to the agreements with AstraZeneca and Sanofi and which are recognized on the basis of the percentage of completion of the works performed by the Company under such agreements:
(i) Revenue from collaboration and licensing agreements for monalizumab decreased by €13.5m to €6.1m in the first half of 2021 (€19.6m in the first half of 2020), due to lower costs in connection with the collaboration works performed relating to the trials’ maturity;
(ii) Revenue from collaboration and licensing agreements for IPH5201 are nil for the first half of 2021 (€8.7m in the first half of 2020), due to the Company having fulfilled all of its commitments on preclinical work related to the start of Phase 1 of the IPH5201 program as of December 31, 2020.
Revenue from invoicing of research and development (R&D) costs for avdoralimab (IPH5401) and IPH5201 are €1.2m the first half of 2021 (€1.1m in the first half of 2020), or an increase of €0.1m, or 11%, between the first half of 2020 and the first half of 2021.
Government funding for research expenditures of €6.4m in the first half of 2021 (€6.9m in the first half of 2020).
Operating expenses are €41.1m in the first half of 2021 (€46.0m in the first half of 2020), of which 53.0% (€21.8m) are related to R&D.
R&D expenses decreased by €9.7m to €21.8m in the first half of 2021 (€31.5m in the first half of 2020). This change mainly results from a decrease in depreciation and amortization expenses allocated to R&D, and a decrease in direct R&D expenses relating to Lumoxiti following the end of the transition period with AstraZeneca in September 2020 and the return of commercialization rights in the U.S. and Europe, as well as the end of recruitment in trials evaluating avdoralimab in oncology.
Selling, general and administrative (SG&A) expenses increased by €4.8m to €19.3m in the first half of 2021 (€14.5m in the first half of 2020) primarily as a result of the provision for charges booked as of June 30, 2021 relating to the payment of $6.2m (€5.2m as of June 30,2021) to be made to AstraZeneca on April 30, 2022. In the full year results 2020 announcement2, the Company reported a contingent liability of up to $12.8m in its consolidated financial statements, which was linked to the split of certain manufacturing costs. As part of the termination and transition agreement, effective on June 30, 2021, Innate and AstraZeneca agreed to split the manufacturing costs, and Innate will pay $6.2m on April 30, 2022.
Revenue from distribution agreement are nil in the first half of 2021 (net gain of €0.9m in the first half of 2020). As of June 30, 2021, following the end of the transition period relating to the commercialization of Lumoxiti in the U.S. on September 30, 2020, the Company recognized net sales of Lumoxiti for the first half of 2021 for an amount of €1.0m.
A net financial gain of €1.7m in the first half of 2021 (net financial loss of €2.0m in the first half of 2020), principally as a result of the decrease in fair value of certain of our financial instruments due to the negative impact of the COVID-19 outbreak on the financial markets in the first half of 2020.
A net loss of €23.7m for the first half of 2021 (net loss of €10.3m for the first half of 2020).

The table below summarizes the IFRS consolidated financial statements as of and for the six months ended June 30, 2021, including 2020 comparative information.

In thousands of euros, except for data per share June 30, 2021 June 30, 2020
Revenue and other income 15,686 36,745
Research and development expenses (21,794) (31,499)
Selling, general and administrative expenses (19,321) (14,490)
Operating expenses (41,115) (45,989)
Net income / (loss) distribution agreements — 896
Operating income (loss) (25,428) (8,348)
Net financial income (loss) 1,709 (1,986)
Income tax expense — —
Net income (loss) (23,719) (10,334)
Weighted average number of shares ( in thousands) : 78,998 78,892
– Basic income (loss) per share (0.30) (0.13)
– Diluted income (loss) per share (0.30) (0.13)

June 30, 2020 December 31, 2020
Cash, cash equivalents and financial assets 159,402 190,571
Total assets 266,217 307,423
Total shareholders’ equity 133,561 155,976
Total financial debt 16,502 19,087
Pipeline highlights:

Lacutamab (anti-KIR3DL2 antibody):

In June 2021, the Company announced promising preliminary data from its Phase 2 TELLOMAK trial, in which lacutamab demonstrated a 35% overall global response rate in patients with mycosis fungoides (MF) that express KIR3DL2 (cohort 2). This first trial data set also established safety and demonstrated skin improvement. Lacutamab reached the pre-determined threshold to advance to stage 2 (six confirmed responses). These results were presented in an oral presentation at the 16th International Conference on Malignant Lymphoma (16-ICML).

In the second half of the year, the Company will initiate two parallel clinical trials to study lacutamab in patients with KIR3DL2-expressing, relapsed/refractory peripheral T-cell lymphoma (PTCL):

Phase 1b trial: a Company-sponsored Phase 1b clinical trial to evaluate lacutamab as a monotherapy in patients with KIR3DL2-expressing relapsed PTCL.

Phase 2 KILT (anti-KIR in T Cell Lymphoma) trial: The Lymphoma Study Association (LYSA) plans to initiate an investigator-sponsored, randomized trial to evaluate lacutamab in combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) versus GEMOX alone in patients with KIR3DL2-expressing relapsed/refractory PTCL.

ANKET (Antibody-based NK cell Engager Therapeutics):

In June 2021, the Company presented new data on its next-generation NK cell engager platform, ANKET, at the Federation of Clinical Immunology Societies (FOCIS) meeting. Specifically, Innate shared data from its tetra-specific ANKET molecule, which is the first NK cell engager technology to engage two NK cell activating receptors (NKp46 and CD16), a cytokine receptor (IL-2Rb) and a tumor antigen via a single molecule. In preclinical studies, the tetra-specific ANKET demonstrated in vitro the ability to induce human NK cell proliferation, cytokine production and cytolytic activity against cancer cells expressing the targeted antigen. The tetra-specific ANKET also demonstrated in vivo anti-tumor efficacy in several tumor models, allowing regression of established tumors as well as control of metastasis, associated with increased NK cell infiltration, cytokine and chemokine production at the tumor site. ANKET also showed a pharmacodynamic effect, low systemic cytokine release and a manageable safety profile in non-human primates.

Progress was made in the IPH6101/SAR443579 collaboration with Sanofi, resulting in the decision announced in January 2021 that Sanofi will transition IPH6101/SAR443579 into investigational new drug (IND)-enabling studies. IPH6101 is a NKp46-based NK cell engager (NKCE) using Innate’s proprietary multi-specific antibody format (Gauthier et al. Cell 2019). The decision triggered a €7 million milestone payment from Sanofi to Innate. In addition, in January 2021, a GLP-tox study was initiated for the IPH6101/SAR443579 program.

The Company will present further ANKET data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 on September 18, 2021.

Monalizumab (anti-NKG2A antibody), partnered with AstraZeneca:

On September 17, 2021, AstraZeneca will present a late-breaker abstract on the COAST Phase 2 trial, highlighting progression-free survival (PFS) results for novel durvalumab combinations with potential new medicines, including Innate’s lead partnered asset, monalizumab, and AstraZeneca’s oleclumab, an anti-CD73 monoclonal antibody, in unresectable, Stage III non-small cell lung cancer at the ESMO (Free ESMO Whitepaper) Congress 2021.

The Company expects to publish data this year from the Phase 2 expansion cohort (‘cohort 3’), exploring the combination of monalizumab, cetuximab and durvalumab in first-line IO naïve patients with R/M SCCHN.

Avdoralimab (IPH5401, anti-C5aR antibody):

In July 2021, the Company announced that FORCE (FOR COVID-19 Elimination), the investigator-sponsored, Phase 2 clinical trial evaluating the safety and efficacy of avdoralimab, in COVID-19 patients with severe pneumonia, did not meet its primary endpoints in all three cohorts of the trial. Results from this trial, including translational data, are planned to be submitted for publication. The Company’s COVID-19 activities were covered by public funding from the French government.
Following a strategic review, the Company will now solely pursue avdoralimab in bullous pemphigoid, an inflammatory disease, through an investigator-sponsored study and stop further development in all other indications.

Corporate Update:

Bpifrance informed Innate that its permanent representative at Innate’s Supervisory Board, Ms. Maylis Ferrere will be replaced by Mr. Olivier Martinez, Senior Investment Director in the Life Sciences Investments Department of the Direction of Innovation of Bpifrance, who has been Observer of Innate’s Supervisory Board since 2010.
Announced on May 28, 2021, Novo Nordisk A/S, represented by Marcus Schindler, M.D., decided not to seek re-election to the Supervisory Board due to Dr. Schindler’s new role as Executive Vice President Research & Early Development and Chief Scientific Officer of Novo Nordisk A/S. Novo Nordisk A/S remains a shareholder in the Company but no longer has a seat on its Supervisory Board.

Pacylex Pharmaceuticals Announces the Initiation of a Phase 1 Clinical of PCLX-001, a First-in-class NMT Inhibitor, in Non-Hodgkin’s Lymphomas and Solid Tumor Patients

On September 14, 2021 Pacylex Pharmaceuticals, Inc. reported that it initiated a Phase 1 clinical trial of PCLX-001, a first-in-class, orally bioavailable small molecule inhibitor of N-myristoyltransferase 1 and 2 (NMT1, NMT2), at the University of Alberta Cross Cancer Institute (Press release, Pacylex Pharmaceuticals, SEP 14, 2021, View Source [SID1234645062]). This open label, dose escalation study will examine the safety and tolerability of PCLX-001 and determine the dose to be used in initial efficacy studies. Pacylex received a No Objection Letter from Health Canada on March 8, 2021, authorizing the planned Phase 1 Trial of PCLX-001 in relapsed/refractory B-cell Non-Hodgkin’s Lymphoma and advanced solid malignancies. PCLX-001 is believed to be the first NMT inhibitor that will be clinically tested.

PCLX-001 is the first clinical candidate sponsored by Pacylex Pharmaceuticals to reach the clinical stage. "We are excited to see PCLX-001 transition to helping serious refractory cancer patients," said Michael Weickert, CEO of Pacylex Pharmaceuticals. "Our mission is to bring this new potential cancer breakthrough to patients, and we are especially privileged to be working with the Cross Cancer Institute on this clinical program."

"We are genuinely excited to initiate a new therapeutic candidate for these very challenging patients," said Dr. John Mackey, the Chief Medical Officer of Pacylex Pharmaceuticals. "Based on its unique mechanism of action and preclinical results, we hope this therapy will provide at least some patients with relief from their disease."

Dr. Randeep Sangha is the principal investigator for the study of PCLX-001 at the Cross Cancer Institute in Edmonton. "We plan to test PCLX-001 on patients who have tried everything else. Testing something really new is the goal of every cancer researcher since it may open the door for new treatments for patients" said Dr. Sangha.

Patient enrollment and dosing will also begin soon at Princess Margaret Hospital in Toronto and the BC Cancer Agency in Vancouver. The study will enroll 20-30 patients in the initial phase. Three principal investigators will oversee the clinical study at the three clinical sites in Canada: Dr. John Kuruvilla at Princess Margaret Cancer Centre in Toronto, Dr. Randeep Sangha at the Cross Cancer Institute in Edmonton, and Dr. Laurie Sehn at the British Columbia Cancer Center in Vancouver.

This study is registered at ClinicalTrials.gov Identifier: NCT04836195.

About Non-Hodgkin’s Lymphoma

Non-Hodgkin’s Lymphoma (NHL) is the most common hematologic malignancy and the eleventh most common cancer worldwide, with nearly 510,000 new cases diagnosed in 2018. It accounted for nearly 249,000 deaths worldwide in 2018. The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.

PCLX-001

PCLX-001 is a small molecule, first-in-class N-myristoyltransferase (NMT) inhibitor, originally developed by the University of Dundee Drug Discovery Unit as part of a program to treat African sleeping sickness funded by Wellcome Trust. Pacylex is developing PCLX-001, which has excellent oral bioavailability, to treat leukemia and lymphoma. PCLX-001 selectively kills cancer cells and completely regresses (eliminates) tumors in animal models of acute myeloid leukemia (AML), diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). PCLX-001 has also been shown to strongly inhibit the growth of lung and breast cancer tumors in animal models. In leukemia, lymphoma and breast cancer patients, the level of NMT2 is correlated with survival, suggesting an important biological role in these cancers. In tests using cultured cancer cells in vitro, PCLX-001 is at least ten times as potent as ibrutinib (Imbruvica) and dasatinib (Sprycel), two clinically approved drugs currently used to treat hematologic malignancies.

Zai Lab Announces Breakthrough Therapy Designation Granted for Bemarituzumab (FPA144) in China

On September 14, 2021 Zai Lab Limited, an innovative commercial-stage biopharmaceutical company, reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) granted Breakthrough Therapy Designation for investigational bemarituzumab (FPA144), for first-line treatment for patients with FGFR2b overexpressing and human epidermal growth factor receptor (HER2)-negative metastatic and locally advanced gastric and GEJ cancers in combination with modified FOLFOX6 (fluoropyrimidine, leucovorin, and oxaliplatin) (Press release, Zai Laboratory, SEP 14, 2021, View Source [SID1234633498]).

"In granting Breakthrough Therapy Designation, we are pleased to see that the CDE recognizes the promise of bemarituzumab. In combination with chemotherapy, bemarituzumab demonstrated clinically meaningful outcomes in key endpoints for patients with advanced gastric or GEJ cancer as a frontline therapy," said Alan Sandler, M.D., president and head of global development, oncology, at Zai Lab. "We look forward to working with regulatory authorities in China as we advance bemarituzumab into global, registrational studies."

The designation is supported by results from the Phase 2 FIGHT study, which evaluated bemarituzumab plus chemotherapy (modified FOLFOX6) versus chemotherapy alone in patients with FGFR2b overexpression, HER2-negative frontline advanced gastric or GEJ cancer. All three efficacy endpoints in the FIGHT trial – PFS, OS and ORR – achieved pre-specified statistical significance in the bemarituzumab arm compared to the placebo arm. Additional analysis showed a positive correlation between benefit and the prevalence of FGFR2b overexpression tumor cells, affirming both the importance of the FGFR2b target and the activity of bemarituzumab against this target. The Breakthrough Therapy Designation was granted based upon this subset of patients, based on IHC testing, showing at least 10% of tumor cells overexpressing FGFR2b.

More than one million new gastric cancer cases are diagnosed annually, and approximately half of all gastric cancer cases occur in China1. Nearly 88% of patients with advanced gastric and GEJ cancers are HER2-negative, and approximately 30% of these patients present with FGFR2b overexpression.

The Breakthrough Therapy Designation review policy is designed to promote the research and creation of drugs with apparent clinical advantages, which are intended for the prevention or treatment of serious life-threatening diseases or diseases which severely impact the quality of life for which there is no existing treatment or where sufficient evidence indicates advantages of the novel drug over currently available treatment options. Drugs that have been granted the Breakthrough Therapy Designation are prioritized by the CDE in communications, and in receiving guidance to promote the drug development progress.

Source: (1) Globocan 2020.

About Bemarituzumab

Bemarituzumab (anti-FGFR2b), also called FPA144, is a potential first-in-class investigational targeted antibody that is designed to block fibroblast growth factors (FGFs) from binding and activating FGFR2b, inhibiting several downstream pro-tumor signaling pathways and potentially slowing cancer progression. Bemarituzumab is being developed in gastric and GEJ cancers as a targeted therapy for tumors that overexpress FGFR2b.

Zai Lab has an exclusive license to develop and commercialize bemarituzumab in Greater China. Zai Lab collaborated with Five Prime (later acquired by Amgen) on the Phase 2 FIGHT trial in Greater China.

Initiation of the registrational program of bemarituzumab by Amgen is planned for the fourth quarter of 2021. Planning is underway for bemarituzumab clinical studies in other solid tumors, including squamous NSCLC.

Skyhawk Therapeutics Completes New Investment Round

On September 14, 2021 Skyhawk Therapeutics, Inc. reported that Fidelity Management & Research Company LLC has led a $133 million oversubscribed investment round in Skyhawk, along with other major investors (Press release, Skyhawk Therapeutics, SEP 14, 2021, View Source [SID1234626568]). This brings total equity funding plus partnership capital in the Company to over $600 million thus far, with potential future milestones of over $20 billion plus ongoing royalties.

"This investment round strengthens Skyhawk’s capacity to advance our internal pipeline of drug candidates deep into the clinic," said Bill Haney, co-founder and CEO of Skyhawk Therapeutics. "We are delighted that investors support our novel platform, a strong foundation from which to advance a series of our internal drugs for patients, even as we expand our work making drug candidates for our pharma collaborators."