On March 23, 2021 Pulmatrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary and non-pulmonary disease using its patented iSPERSE technology, reported its Q4 and full year 2020 financial results and provides a business update (Press release, Pulmatrix, MAR 23, 2021, View Source [SID1234576998]).

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"In recent months, we have made important progress advancing iSPERSE enabled programs that both strengthen our foundation in respiratory indications and expand the reach of our platform to lung cancer and acute migraine," said Ted Raad, Chief Executive Officer of Pulmatrix. "Our strengthened balance sheet fully funds our operations through key data milestones across our ongoing and planned studies including the PUR1800 Phase 1b study, the PUR3100 Phase 1 / Phase 2 study and Pulmazole Phase 2b study. We look forward to a milestone rich 2021 which includes toxicology and clinical data packages from ongoing PUR1800 studies, potential license option execution from Johnson & Johnson, and continued execution as we advance therapies to address significant unmet need."

Q4 and Recent Highlights:

PUR1800

Initiated the Phase 1b clinical study of PUR1800, dosing 4 of 15 patients to date. Study endpoints include safety, tolerability and exploratory biomarkers to demonstrate target engagement and anti-inflammatory effect. Ph1b top-line data is expected in Q4 2021, shortly after data from 6 and 9-month toxicology studies.
Completion of the PUR1800 Phase 1b will trigger a $2M milestone payment as part of the kinase inhibitor licensing and development agreement with the Lung Cancer Initiative (LCI) at Johnson & Johnson*, which was previously on January 2, 2020.
Pulmazole

Successfully completed a Type C Meeting with the U.S. FDA for the further clinical development of Pulmazole.
Based on feedback from the Type C Meeting, and in accordance with our collaboration with Cipla, Pulmatrix intends to initiate a Phase 2b clinical study of Pulmazole in allergic bronchopulmonary aspergillosis (ABPA) in Q1 2022, dependent on assessment of COVID-19 impact on patient safety and study operations.
PUR3100

Declared PUR3100 development candidate, a dry powder iSPERSE formulation of DHE for pulmonary delivery in acute migraine.
Completed dog PK study of PUR3100, demonstrated similar exposure kinetics to modelled kinetics from published data with MAP0004, the MAP Pharmaceuticals pMDI inhaled formulation of DHE.
Progressing IND-enabling studies with Phase 1/Phase 2 clinical study anticipated to begin Q1 2022.
Corporate:

Completed a registered direct offering with gross proceeds of $40 million extending the Company’s cash through data readouts across its development pipeline including PUR1800 Phase 1b, PUR3100 Phase 1 / Phase 2, and Pulmazole Phase 2b studies.
Financials

As of December 31, 2020, Pulmatrix had $31.7 million in cash and cash equivalents, compared to $23.4 million for the year ended December 31, 2019.

Revenue for 2020 was $12.6 million, compared to $7.9 million for 2019. The increase resulted from an increase in revenue recorded of $6.9 million as a result of the JJEI License Agreement and includes reimbursement of pass-through expenses, partially offset by a decrease in revenue recorded of $2.2 million as a result of the Cipla Agreement.

Research and development expense was $15.6 million in 2020 compared to $12.8 million in 2019. The increase year–over–year was primarily due to increased spending on manufacturing, clinical, and preclinical study costs of $4.4 million and $0.3 million, on the PUR1800 and PUR3100 programs, respectively, $1.1 million on employment costs in support of our programs, $0.6 million in allocated fixed expenses and lab services which were partially offset by a decrease of $3.6 million on the Phase 2 Pulmazole clinical trial costs.

General and administrative expense was $6.9 million for 2020 and $8.5 million for 2019. The decrease year-over-year was primarily due to decreased employment costs of $1.2 million because of lower share-based compensation expense and salary costs, $0.1 million in patent and legal expenses and $0.3 million of a milestone payment to the CFFT made in 2019.

Goodwill was not impaired in 2020 compared to a $7.3 million impairment charge in 2019.

Net loss for 2020 was $19.3 million. The net loss in 2020 was primarily attributable to Pulmazole project costs as we advanced our Phase 2 clinical study and PUR1800 manufacturing, preclinical, and clinical study costs for the upcoming Phase 1b clinical study.

On March 23, 2021 Incyte (Nasdaq:INCY) reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Pemazyre (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene1, worsening after cancer chemotherapy (Press release, Incyte, MAR 23, 2021, View Source [SID1234576994]).

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"The MHLW approval of Pemazyre is an important milestone for the BTC community, and underscores our commitment to finding and delivering solutions for patients with significant unmet medical needs," said Lothar Finke, M.D., Ph.D., General Manager, Incyte Asia. "BTC is a rare and serious condition, and we are proud that with the support of the MHLW we will be able to bring a new targeted treatment to more patients around the world."

BTC is a rare cancer that forms in the bile duct. Cholangiocarcinoma, a subtype of BTC, is classified based on its origin: intrahepatic, which occurs in the bile duct inside the liver and extrahepatic, which occurs in the bile duct outside the liver. Patients with BTC are often diagnosed at a late or advanced stage when the prognosis is poor2,3. FGFR2 fusions or rearrangements, which occur almost exclusively in intrahepatic cholangiocarcinoma, are observed in a small percentage of Japanese patients with BTC4,5,6,7.

The approval is based on data from the FIGHT-202 study evaluating the safety and efficacy of pemigatinib in adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status. In FIGHT-202 patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% (primary endpoint), and median DOR of 7.49 months (secondary endpoint). The most frequent treatment-emergent adverse event (TEAE) were grade ≤2 hyperphosphatemia (58.2%). Other frequent TEAEs (all grades) observed in ≥30% of patients were alopecia, diarrhea, fatigue, dysgeusia, nausea, constipation, stomatitis, dry mouth and decreased appetite. The majority of these TEAEs were grade ≤2. The TEAE with grade ≥3 that occurred in ≥10% of patients was hypophosphatemia.

Previously, the MHLW granted Orphan Drug Designation for Pemazyre – a designation granted to investigational compounds intended to treat rare diseases that affect fewer than 50,000 people in Japan, and for which there is a high medical need8. Designated orphan drugs are eligible for priority review for marketing authorizations to ensure supply to clinical settings at the earliest opportunity8.

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) 1, 2, 3 inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg pemigatinib orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of pemigatinib therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating pemigatinib in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type.

FIGHT-302 is a Phase 3 study investigating pemigatinib as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About Pemazyre (pemigatinib)

Pemazyre is a kinase inhibitor indicated in the United States for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test9. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Japan, Pemazyre is approved for the treatment of patients with unresectable biliary tract cancer (BTC) with a fibroblast growth factor receptor 2 (FGFR2) fusion gene, worsening after cancer chemotherapy.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States and will be marketed by Incyte in Japan. Incyte has granted Innovent Biologics, Inc. rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.

Additionally, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the conditional marketing authorization of pemigatinib for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy.

Pemazyre is a trademark of Incyte Corporation.

On March 23, 2021 Oxford Vacmedix, the UK-based biopharma company focused on the development of cancer vaccines reported the appointment of Dr. Thomas Morris BSc, MB BCh, LlM, MRCP FFPM as Chief Medical Officer (Press release, Oxford Vacmedix, MAR 23, 2021, View Source [SID1234576993]). Tom originally worked as a physician in the NHS before joining industry, including many years at Astra Zeneca where he led the global clinical development of several oncology compounds. He has been responsible for the design, implementation and subsequent analysis of many study protocols, including several first in man clinical trials. Tom has wide experience in scientific interactions and in negotiation with the US, European and Japanese regulatory agencies on clinical development plans pre-phase III.

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William Finch, Chief Executive Officer of Oxford Vacmedix said;
"I am delighted to welcome Tom to the team at Oxford Vacmedix at this critical time, as move our lead cancer vaccine, OVM-200, into the clinic. His extensive experience in oncology and in clinical development will be invaluable for the next phase of the development of our vaccines as monotherapy and in combination with immune-oncology agents, to meet the needs of cancer patients."

Dr Morris qualified in Physiology and Medicine from the University of Wales in 1987 and went on to gain a master’s degree in Law from the University of Cardiff. He was awarded the Fellowship of the Faculty of Pharmaceutical Medicine from the Royal College of Physicians in 2003 and was appointed to the role of Registrar and Board Member of the Faculty in 2015. Tom also served as a member of the Faculty’s Coordination Committee and as a Speciality Adviser, responsible for overseeing training in pharmaceutical medicine, and was previously Chair of the Ethical Issues Committee and member of the Professional Standards Committee of the Faculty.

Tom Morris commented;
"I am very pleased to be joining Oxford Vacmedix to lead the clinical development of these novel cancer vaccines. The underlying ROP technology offers great hope to provide safe and effective therapies to help people with cancer live longer and better lives, and I look forward to making a positive contribution to the company."

On March 23, 2021 Novartis reported the first interpretable results of the Phase III VISION study evaluating the efficacy and safety of 177Lu-PSMA-617, a targeted radioligand therapy in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) compared to best standard of care alone (Press release, Novartis, MAR 23, 2021, View Source [SID1234576992]). The trial met both primary endpoints of overall survival and radiographic progression-free survival1, helping to move closer the ambition of becoming the targeted treatment for >80% of patients with advanced prostate cancer. The safety profile was consistent with data reported in previous clinical studies1. Results from the VISION trial will be presented at an upcoming medical meeting and included in US and EU regulatory submissions.

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"Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years2 and need new treatment options. These groundbreaking data confirm our belief in the potential of 177Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine. We intend to submit these data to regulatory authorities as soon as possible," said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. "We would like to thank the patients who volunteered to participate in this study as well as the clinical teams at each of the trial sites. We would not be able to realize our commitment to reimagining medicine without the partnership of patients and their families."

Radioligand therapy combines a targeting compound that binds to markers expressed by tumors and a radioactive isotope, causing DNA damage that inhibits tumor growth and replication. This therapeutic approach enables targeted delivery of radiation to the tumor, while limiting damage to the surrounding normal tissue. Novartis has established global expertise and specialized supply chain and manufacturing capabilities across its network of four radioligand therapy production sites, and is further increasing capacity to ensure delivery of radioligand therapies like 177Lu-PSMA-617 to patients in need.

Novartis is the only pharmaceutical company which is pursuing four different cancer treatment platforms. These include radioligand therapy, cell and gene therapy, and targeted therapy and immunotherapy, with an opportunity to combine these platforms for the best outcomes for each cancer patient.

About Advanced Prostate Cancer
Prostate cancer is a form of cancer that develops in the prostate gland, a small walnut shaped gland in the pelvis of men. In castration resistant prostate cancer (CRPC), the tumor shows signs of growth, such as rising Prostate Specific Antigen (PSA) levels, despite the use of hormone treatments that lower testosterone3. In metastatic CRPC (mCRPC), the tumor spreads to other parts of the body, such as neighboring organs or bones and remains unresponsive to hormone treatment4. The five-year survival rate for patients with mCRPC is approximately 15%2.

About Phenotypic Precision Medicine in Advanced Prostate Cancer
Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with metastatic castration resistant prostate cancer. More than 80% of prostate cancer tumors highly express a phenotypic biomarker5 called Prostate Specific Membrane Antigen (PSMA)4,6-9, making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy6.

About 177Lu-PSMA-617
177Lu-PSMA-617 is an investigational PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. It is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle)10-12. After administration into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells that express PSMA13, a transmembrane protein, with high tumor-to-normal tissue uptake10,14,15. Once bound, emissions from the radioisotope damage tumor cells, disrupting their ability to replicate and/or triggering cell death. The radiation from the radioisotope works over very short distances to limit damage to surrounding cells14,16.

About VISION
VISION is an international, prospective, randomized, open-label, multicenter, phase III study to assess the efficacy and safety of 177Lu-PSMA-617 (7.4 GBq administered by i.v. infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen best standard of care in the investigational arm, versus best standard of care in the control arm17. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and androgen receptor-directed therapy (ARDT), were randomized in a 2:1 ratio in favor of the investigational arm. The alternate primary endpoints were rPFS and OS. The study enrolled 831 patients1.

On March 22, 2021 Nuformix plc (LSE:NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, reported that Oxilio Ltd ("Oxilio") has exercised its option to acquire a licence for NXP001 (a proprietary new form of aprepitant) for oncology indications (Press release, Nuformix, MAR 22, 2021, View Source [SID1234621610]).

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· On 23 September 2020, Nuformix granted an exclusive option to Oxilio, a private pharmaceutical development company, to license NXP001 globally for oncology indications. This triggered the first upfront payment and the option period ran until 23 March 2021
· Nuformix and Oxilio will now work together to finalise a global licensing agreement for NXP001. Once this has been agreed, this will trigger a second undisclosed upfront payment, payable to Nuformix. Under this agreement, Nuformix will license its patent estate and know-how on NXP001 in return for development milestone payments and a royalty on any future net sales, capped at £2m per annum

Dr Anne Brindley, CEO of Nuformix, said: "We are very pleased that Oxilio has exercised its option for NXP001, allowing them to continue the development of NXP001 in oncology. We will now look to finalise the licensing agreement with Oxilio that will provide Nuformix with near term revenue and an opportunity to benefit from the upside of the significant global oncology market. This successful outcome endorses the Nuformix strategy of identifying new improved forms of existing drugs for repurposing into new indications with early-stage licensing during the pre-clinical or Phase 1 stages of development."

Dr Simon Yaxley, Co-Founder and Director of Oxilio said: "Exercising our option gives us the opportunity to continue to develop NXP001 in line with our approach to optimise the delivery of our drug for the effective treatment of certain cancers. We look forward to continuing our collaboration with Nuformix to realise the huge potential of this approach."

About NXP001
NXP001 is a proprietary new form of the drug aprepitant that is currently marketed as a product in the oncology supportive care setting (chemotherapy induced nausea and vomiting). A disadvantage of aprepitant is that its suboptimal properties necessitate a complex formulation. Nuformix discovered new forms of aprepitant (NXP001) with improved properties and it has granted patents on its new forms.

About NXP001 and Oxilio
Oxilio will develop and seek to exploit NXP001 globally for the treatment of cancer. Cancer is one of the world’s primary causes of death. The total worldwide annual economic cost of cancer is substantially in excess of US$1 trillion. Traditional cancer treatments such as surgery, chemotherapy and radiotherapy are expensive and often have debilitating consequences for the patient. Costs of cancer drug treatments are also increasing, in large part due to the expense of taking new drugs through clinical trials where historically there is a very low rate of success. Therefore, there is an urgent need to develop safe, effective, and readily available anticancer agents.

Oxilio is focused on alleviating the current dilemma of a shortage of effective drug candidates that have potential as new cancer therapies, by adopting a drug repurposing strategy (identifying new uses for approved or investigational drugs that are outside the scope of the original medical indication). The major advantage of this approach is that the pharmacokinetics, pharmacodynamics and toxicity profiles of these drugs are already reasonably well established. Thus, drug repurposing is a less risky development route with substantially lower associated development costs. The agreement with Nuformix allows Oxilio to focus on developing rapidly a unique formulation and dosage form with NXP001 and progressing into the clinic.

Oxilio is a privately held pharmaceutical development company focused on repurposing known drugs for the treatment of cancer through a programme of corporate alliances coupled with rapid proof of concept clinical development.