On November 16, 2021 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported that the results from a Phase 1 trial evaluating multiple ascending doses and the food effect of LYT-100 (deupirfenidone) were published in the journal Clinical Pharmacology in Drug Development (Press release, PureTech Health, NOV 16, 2021, View Source [SID1234595701]). Topline results from this Phase 1 study were previously announced in November 2020 and demonstrated that LYT-100 was well-tolerated in healthy volunteers under both fed and fasting conditions.

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LYT-100 is PureTech’s wholly-owned therapeutic candidate that is being advanced for the potential treatment of conditions involving inflammation and fibrosis and disorders of lymphatic flow. It is currently being evaluated in two Phase 2 trials in patients with Long COVID respiratory complications and breast cancer-related, upper limb secondary lymphedema. Enrollment in the Long COVID respiratory trial is expected to be completed by the end of 2021, with topline results anticipated in the first half of 2022. Topline results from the breast cancer-related, upper limb secondary lymphedema trial are anticipated in 2022.

"The data set from the completed Phase 1 MAD study, including a favorable safety and tolerability profile, reaffirms our belief that LYT-100 has the potential to be an attractive therapeutic option across a range of conditions. There are substantial shortcomings with the current standards of care for patients living with fibrotic lung disease, and we believe that the anti-fibrotic and anti-inflammatory properties along with the favorable tolerability profile demonstrated with LYT-100 to date could address this issue," said Michael Chen, Ph.D., Head of Innovation at PureTech Health. "We’re encouraged by these results and look forward to the upcoming clinical readouts as we advance LYT-100 in multiple indications."

LYT-100 is a selectively deuterated form of pirfenidone that retains the pharmacologic properties of the parent compound but is expected to be metabolized at an attenuated rate. GI-related tolerability issues have historically been associated with pirfenidone and have limited its usage in patients at the therapeutic dose approved by the U.S. Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF). Despite a noted dose-efficacy response in clinical trials in patients with IPF, higher doses of pirfenidone have not been adequately explored due to limitations in tolerability. PureTech is currently exploring the pharmacokinetic (PK) and tolerability profile of LYT-100 across a range of doses in order to determine whether LYT-100 can achieve higher levels of systemic exposure than the currently FDA-approved dose of pirfenidone.

Multiple ascending dose and food effect study results

The Phase 1 multiple ascending dose and food effect study was a randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, PK profile and food effect of LYT-100 in healthy volunteers in both fed and fasting states. Plasma concentrations of LYT-100 and its metabolites were measured to determine PK parameters.

Part 1 assessed multiple ascending doses of LYT-100 administered in doses of 100 mg, 250 mg, 500 mg, 750 mg and 1000 mg BID over five days without dose titration. Part 2 assessed the effect of fed versus fasting conditions on the PK profile of LYT-100 following a single 500 mg dose. No dose limiting toxicities were noted, and a maximum tolerated dose was not determined.

All adverse events (AEs) that were possibly or probably related to LYT-100 were mild. Of the 40 participants, 37 (92.5%) completed part 1 of the study and eight participants who completed part 1 also completed part 2. The most common AEs across part 1 of the multiple ascending dose cohorts were headache, abdominal distension and nausea. There were no tolerability issues after administration of a single dose of 500 mg given with or without food.

A dose-proportional PK profile was observed with LYT-100 throughout the range of doses studied. As with pirfenidone, LYT-100 exposure was affected by food, with fed conditions resulting in lower drug exposure compared to fasting conditions. The ratio of exposure during fed conditions was approximately 20% to 25% less than exposure during fasting. Fed conditions led to a 26% reduction in Cmax observed with LYT-100, while the Cmax reduction stated in the ESBRIET (pirfenidone) U.S. Prescribing Information is 49%.

The therapeutic dose of pirfenidone approved by the FDA for the treatment of IPF is 801 mg three times a day. LYT-100 is designed to potentially improve upon this regimen. In a previously conducted single-dose crossover study, an 801 mg dose of LYT-100 resulted in greater drug exposure than an 801 mg dose of pirfenidone. In part 1 of the multiple ascending dose study, LYT-100 was well-tolerated at a dose above 801 mg.

Additional Phase 1 studies and future development plans

Given that the maximum tolerated dose for LYT-100 was not determined in the original Phase 1 study, PureTech initiated a second multiple ascending dose study earlier this year to evaluate higher doses of the drug in healthy volunteers. PureTech also initiated additional Phase 1 studies to further evaluate the PK, dosing and tolerability of LYT-100 in healthy volunteers and healthy older adults to inform the clinical development of LYT-100 across multiple indications. Results from these studies are expected in the first quarter of 2022.

About LYT-100

LYT-100 is PureTech’s most advanced therapeutic candidate from within its Wholly Owned Pipeline. A deuterated form of pirfenidone, an approved anti-inflammatory and anti-fibrotic drug, LYT-100 is being advanced for the potential treatment of conditions involving inflammation and fibrosis, including lung disease (e.g., IPF and potentially other PF-ILDs and Long COVID respiratory complications and related sequelae), and disorders of lymphatic flow, such as lymphedema. PureTech is also exploring the potential evaluation of LYT-100 in other inflammatory and fibrotic conditions such as myocardial, kidney and other organ system fibrosis based on clinical data around the use of pirfenidone in these indications.

PureTech completed a Phase 1 multiple ascending dose and food effect study evaluating LYT-100 in healthy volunteers and found it to be well-tolerated at all doses tested. In the fourth quarter of 2020, PureTech initiated a Phase 2 trial evaluating LYT-100 as a potential treatment for Long COVID respiratory complications and related sequalae and a Phase 2a proof-of-concept study evaluating LYT-100 in patients with breast cancer-related, upper limb secondary lymphedema. PureTech has also initiated additional Phase 1 clinical trials to further explore the PK, dosing and tolerability of LYT-100 in healthy volunteers. Results from these trials are expected to provide additional supportive data to inform the clinical development of LYT-100 across multiple indications.

1 Long COVID is a term being used to describe the emerging and persistent complications following the resolution of COVID-19 infection, also known as post-acute COVID-19 syndrome (PACS).

On November 16, 2021 Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) ("Innate" or the "Company") reported its revenues and cash position for the first nine months of 2021 (Press release, Innate Pharma, NOV 16, 2021, View Source [SID1234595699]).

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"In the period, we continued to execute against our strategic priorities as we reported readouts from two of our partnered portfolio programs. This included randomized Phase 2 data for monalizumab in combination with durvalumab in unresectable, Stage III NSCLC as well as pre-clinical data from our lead ANKET molecule targeting CD123 in acute myeloid leukemia. These readouts continue to 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. "Looking ahead, we will continue to advance our lacutamab development program and move our early-stage R&D activities towards the clinic with our next generation ANKET platform. We also look forward to seeing AstraZeneca’s upcoming plans for monalizumab’s registrational study in unresectable, Stage III NSCLC, which further reinforces our strategy of building a sustainable business with a robust R&D engine."

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 following the event.

Pipeline highlights:

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

In September, AstraZeneca presented a late-breaker abstract on the randomized COAST Phase 2 trial in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress. The presentation highlighted progression-free survival (PFS) and overall response rate (ORR) results for durvalumab in combination with monalizumab, Innate’s lead partnered asset, and oleclumab, AstraZeneca’s anti-CD73 monoclonal antibody. After a median follow-up of 11.5 months, the results of an interim analysis showed a 10-month PFS rate of 72.7% for durvalumab plus monalizumab, versus 39.2% with durvalumab alone in unresectable, Stage III NSCLC patients following chemoradiation therapy. The results also showed an increase in the primary endpoint of confirmed ORR for durvalumab plus monalizumab over durvalumab alone (36% vs. 18%).
Based on the data, AstraZeneca announced plans to initiate a Phase 3 trial for both combinations of monalizumab or oleclumab plus durvalumab in the unresectable, Stage III NSCLC setting for patients who had not progressed after concurrent chemoradiation therapy.
Separately, AstraZeneca also announced that it is starting a Phase 2 clinical trial, NeoCOAST-2, that includes a treatment arm with durvalumab in combination with chemotherapy and monalizumab in resectable, early-stage NSCLC.
Innate will present data from the Phase 2 expansion cohort (‘cohort 3’), exploring the combination of monalizumab, cetuximab and durvalumab in first-line IO naïve patients with recurrent/metastatic squamous cell carcinoma of the head and neck, which was accepted as a mini oral presentation at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (ESMO-IO) conference in December 2021.
Lacutamab (anti-KIR3DL2 antibody):

Two parallel clinical trials to study lacutamab in patients with KIR3DL2-expressing, relapsed/refractory peripheral T-cell lymphoma (PTCL) are initiating:
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):

IPH6101/SAR443579

In November Innate and Sanofi shared new data on IPH6101/SAR443579 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) conference. IPH6101/SAR443579 is the first NKp46/CD16-based NK cell engager using Innate’s proprietary ANKET multispecific antibody format that targets CD123 on acute myeloid leukemia (AML) cells and co-engages NKp46 and CD16a on NK cells.

IPH6101/SAR443579 demonstrated potent antitumor activity against AML cell lines and primary AML blasts, including those resistant to ADCC by a comparator anti-CD123 antibody. IPH6101/SAR443579 also promoted strong and specific NK-cell activation and induced cytokine secretion only in the presence of AML target cells. In addition, IPH6101/SAR443579 had sustained pharmacodynamic effects in non-human primates, combining efficient depletion of CD123-expressing cells with minor cytokine release and a favorable safety profile in comparison to T-cell engagers.
Tetra-specific ANKET

In September and November 2021, Innate also presented at the ESMO (Free ESMO Whitepaper) 2021 and SITC (Free SITC Whitepaper) conferences respectively. 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.
IPH5201 (anti-CD39):

AstraZeneca is conducting a Phase 1 trial in solid tumors with IPH5201 alone or in combination with durvalumab. The data is expected to be presented in 2022.
IPH5301 (anti-CD73):

The Company is initiating an investigator-sponsored Phase 1 trial of IPH5301 in collaboration with the Institut Paoli-Calmettes.
Financial Results:

Cash, cash equivalents and financial assets of the Company amounted to €141.8 million as of September 30, 2021. At the same date, financial liabilities amounted to €16.1 million.

Revenues for the first nine months of 2021 amounted to €10.3 million (€33.6 million for the same period in 2020). For the nine-month period, ended September 30, 2021, revenue from collaboration and licensing agreements mainly results from the spreading of the payments received under our agreements with AstraZeneca and Sanofi.

On November 16, 2021 Viewpoint Molecular Targeting, Inc. ("Viewpoint" or the "Company"), a radiopharmaceutical company developing precision lead-212-based α-particle oncology therapeutics and complementary diagnostic imaging agents, reported it has entered into a Memorandum of Understanding (MoU) with The National Nuclear Laboratory (NNL) to explore avenues to supply Pb-212 to researchers, and possibly clinicians, in the United Kingdom and Europe, using Viewpoint’s proprietary isotope generator, VMT- -GEN (Press release, Viewpoint Molecular Targeting, NOV 16, 2021, https://viewpointmt.com/viewpoint-molecular-targeting-enters-agreement-with-uk-based-national-nuclear-laboratory-ltd-to-advance-development-of-targeted-alpha-therapy-for-cancer/ [SID1234595698]).

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VMT- -GEN is an elegantly-designed isotope generator that provides therapeutic doses of Pb-212 for the Company’s therapeutics – part of its ("Theranostic") programs for the treatment of cancers (including metastatic melanoma, neuroendocrine tumors, and other oncology indications in the company pipeline).

"This agreement is great news for the UK nuclear medicine research community and ultimately, cancer patients. Targeted radionuclide therapy with alpha-emitting radionuclides such as actinium-225 has shown some astonishing success in early small-scale trials for treating cancer patients recently, but availability of these radionuclides is a major roadblock to implementing it more widely, particularly in the UK. The availability of lead-212 made possible by this collaboration will go a long way to removing this roadblock, allowing the UK’s world-leading radiochemistry, radiobiology and clinical researchers to develop new treatments for cancer," added Phil Blower, DPhil, FRSC, Professor of Imaging Chemistry, KCL, Head of Dept of Imaging Chemistry and Biology.

The National Nuclear Laboratory is a UK government owned and operated nuclear services technology provider covering the whole of the nuclear fuel cycle. As part of the agreement, Viewpoint and NNL will explore opportunities for the provision of feedstock radionuclides at the appropriate specification for production of VMT-α-GEN generators; and the use of laboratory facilities required for the production of generators in the UK.

"This agreement with NNL is a momentous step forward as we work to deploy our proprietary VMT- -GEN generator and thereby expand the global availability of lead-212. We believe our VMT- -GEN holds a tremendous amount of potential and this collaboration enables us to supply lead-212 to support preclinical work and clinical trials utilizing VMT-α-GEN in the United Kingdom," commented Michael K. Schultz, PhD, Chief Science Officer of Viewpoint. "We are committed to bolstering our networks with researchers as well as distribution in the UK and Europe to optimize that potential. We are honored to be working with the NNL team and look forward to leveraging their knowledge and expertise."

Radionuclide generators such as VMT- -GEN are used commonly in radiopharmaceutical manufacturing operations and nuclear medicine facilities across the world. The devices share a common characteristic of enabling the production of a purified chemical form of the radionuclide needed that can be easily combined with ligands that seek out cancerous tumors. Because the shelf life of VMT- -GEN is based on longer-lived radionuclides, a single shipment of VMT- -GEN can be used to produce radiopharmaceutical doses daily, for up to a week or more. Given their small footprint, multiple generators can easily be operated within a single facility simultaneously. The device also simplifies radioactive waste management as the spent generator can be easily returned to the manufacturer in approved packaging to eliminate radioactive waste from the medical center or radiopharmacy.

On November 16, 2021 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, NOV 16, 2021, View Source [SID1234595697]):

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Evercore ISI 4th Annual HealthCONx Conference at 9:15 a.m. ET on Tuesday, November 30, 2021
Piper Sandler 33rd Annual Healthcare Conference at 8:00 a.m. ET on Wednesday, December 1, 2021
The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays of the webcasts will be archived on the Company’s website for at least 30 days.

On November 16, 2021 Purple Biotech Presented the Corporate Presentation (Presentation, Purple Biotech, NOV 16, 2021, View Source [SID1234595696])

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