On May 13, 2021 Savara Inc. (Nasdaq: SVRA), a clinical stage biopharmaceutical company focused on rare respiratory diseases, reported financial results for the first quarter ending March 31, 2021 and provided a business update (Press release, Savara, MAY 13, 2021, View Source [SID1234580041]).

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 made considerable progress in the first quarter of the year," said Matt Pauls, Chair and Chief Executive Officer, Savara. "This includes the strategic decision to wind down two pipeline programs, enabling us to focus solely on advancing our lead asset, molgramostim in aPAP. Additionally, we started the onboarding process of a global, full-service contract research organization that is partnering with us to execute the IMPALA-2 trial. Lastly, we strengthened our cash position through a $130M equity raise. With a balance sheet of approximately $193M, we believe our runway extends through 2025 – well beyond the expected top line results of IMPALA-2 in 2Q 2024."

"We are pleased to announce that the IMPALA-2 site activation process has begun," said Badrul Chowdhury, Chief Medical Officer, Savara. "Sites will be activated on a rolling basis, with approximately 10-15 expected to be active by the end of June. As sites launch, patients are evaluated, and those who are eligible will begin a six-week screening period. This means patients could be randomized and dosed by the end of 2Q or early 3Q 2021. We also recently strengthened our management team with the hire of Dr. Dhaval Desai as Head of Clinical Development and Brian Maurer as Head of Clinical Operations. Both are seasoned professionals with deep expertise in running global clinical trials."

First Quarter Financial Results (Unaudited)

Savara’s net loss attributable to common stockholders for the three months ended March 31, 2021 was $10.2 million, or $(0.13) per share, compared with a net loss attributable to common stockholders of $15.4 million, or $(0.27) per share, for the three months ended March 31, 2020.

Research and development expenses decreased by $5.6 million, or 42.5%, to $7.6 million for the three months ended March 31, 2021 from $13.2 million for the three months ended March 31, 2020. The decrease is largely attributable to $5.4 million of costs for the acquisition of inhaled liposomal ciprofloxacin (Apulmiq) in March 2020. There were no research and development costs incurred related to Apulmiq during the three months ended March 31, 2021.

General and administrative expenses decreased by approximately $0.2 million, or 6.8%, to $2.8 million for the three months ended March 31, 2021 from $3.0 million for the three months ended March 31, 2020. This was primarily due to a decrease in noncash stock-based compensation and personnel costs for the three months ended March 31, 2021.

As of March 31, 2021, Savara had cash, cash equivalents, and short-term investments of approximately $192.7 million and debt of approximately $25 million.

Pulmatrix has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-K/A [Amend], Pulmatrix, 2021, MAY 14, 2021, View Source [SID1234580083]).

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!

On May 13, 2021 Certara, Inc. (Nasdaq: CERT), the global leader in biosimulation, reported the launch of new versions of its Immunogenicity (IG) and Immuno-oncology (IO) Quantitative Systems Pharmacology (QSP) Simulators to help address the challenges in the development of biologics and cancer Therapies (Press release, Certara, MAY 13, 2021, View Source [SID1234579906]). These new versions further expand applications of QSP and advance the field of using virtual patients to conduct computer-based trials throughout drug discovery and development.

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 have seen an increasing interest in the potential of QSP to guide regulatory decisions and anticipate that this will only continue to grow, much like physiologically-based pharmacokinetic (PBPK) modeling, which is now a critical component in many regulatory submissions," said William F. Feehery, Ph.D., CEO of Certara.

QSP addresses the most complex challenges in drug development by combining computational modeling and experimental data to examine the relationships between a drug, biological system, and disease process. Immunogenicity is a key challenge for developing biologics, including novel modalities such as gene and cell therapies. Researchers use Certara’s IG Simulator to simulate immunogenicity in virtual patients. Version 4.0 of the IG Simulator now allows for the extrapolation of ex vivo patient assays in addition to in vitro assays to better inform the model and predict clinical outcomes. The IG Simulator has now been used in more than 20 case examples. Certara and its customers will be presenting several of these case examples at an upcoming FDA workshop in June.

In immuno-oncology, the sheer number of possible therapy combinations requires a quantitative framework to integrate the complex and dynamic factors that determine efficacy and historically have led to the selection of suboptimal combinations. Certara’s IO Simulator uses virtual patients to quickly test these different combinations to determine the optimal combination of therapies and dosing regimens. Version 3.0 of the IO Simulator vastly expands the number of targets and cell types including cytokines, immune cell types, and tumor neoantigens. It can also now test combinations of chemotherapy and radiotherapy. The IO Simulator has correctly predicted therapeutic outcomes of using drugs in various cancer types, including solid tumors and blood cancers.

"QSP is demonstrating its capacity to improve biopharmaceutical R&D, improving confidence in both the drug compound and target to increase the likelihood of success," said Piet van der Graaf, Ph.D., Senior Vice President, QSP at Certara. "The IG Simulator can use first-in-human data to design Phase II/III trials, predict impact of disease and co-medication, extrapolate to new populations, and predict if IG can be managed via dosing regimens. In tandem with the rise of IO therapeutics, we’ve expanded the number of drug targets and cell types in our IO Simulator enabling us to better predict optimal drug combinations and dosing regimens for more patient populations."

In recent years, the emergence of QSP has attracted increasing interest and is now becoming an essential part in model-informed drug discovery and development. The U.S. Food and Drug Administration (FDA) has seen an increase in evaluating QSP approaches in regulatory submissions.

On May 13, 2021 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported financial results for the first quarter ending March 31, 2021 and provided a regulatory update on lenzilumab (Press release, Humanigen, MAY 13, 2021, View Source [SID1234579922]).

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 are encouraged by the achievements Humanigen has made since the beginning of 2021 and by our progress on the emergency use authorization application," stated Cameron Durrant, MD, MBA, Chief Executive Officer, Humanigen. "We successfully completed our Phase 3 study of lenzilumab, referred to as LIVE-AIR, for the treatment of newly hospitalized and hypoxic COVID-19 patients. Trial results showed that patients who received lenzilumab and other treatments, including steroids and/or remdesivir, had a 54% greater relative likelihood of survival without the need for IMV compared with patients receiving placebo and other treatments. We believe this statistically significant result, along with data regarding additional endpoints and further analysis from the study, support the submission of applications for emergency use authorization to the U.S. Food and Drug Administration and conditional marketing authorization in the United Kingdom and the European Union. As is typical with COVID-19 study results, a pre-print of the LIVE-AIR study was published on-line. Positive results from the Phase 1b study of lenzilumab in combination with CAR-T gave further encouragement to our therapeutic approach to breaking the linkage between efficacy and toxicity in CAR-T, and we are designing a Phase 2 study of lenzilumab combined with all commercially available CD19 CAR-T therapies in diffuse large B-cell lymphoma patients."

Highlights from the First Quarter of 2021 Include:

Clinical – Lenzilumab in COVID-19

The Phase 3 results from the LIVE-AIR study were announced, demonstrating that lenzilumab improves survival without the need for mechanical ventilation in hospitalized, hypoxic patients with COVID-19.
Results from the LIVE-AIR Phase 3 study were published in MedRxiv, (View Source) showing additional analysis from the trial, including patients treated with remdesivir and/or steroids, and a second analysis which showed patients under 85 years of age with C-reactive protein ("CRP"), a widely-utilized inflammatory marker, less than 150 mg/L, derived the greatest benefit of treatment with lenzilumab.
With the report of positive top-line results from the LIVE-AIR study in March 2021, the company met the first of two specified milestones under the South Korea license agreement with KPM Tech Co., Ltd. and its affiliate, Telcon RF Pharmaceutical, Inc., and received $6.0 million (or $4.5 million net of withholding taxes and other fees and royalties) in the second quarter of 2021.
In preparation for potential launch under emergency use authorization ("EUA") and conditional marketing authorization ("CMA"), Humanigen entered into several supply agreements with contract manufacturing organizations ("CMOs") to supply bulk drug, fill/finish, and commercial packaging.
Clinical – CAR-T and Oncology

The positive data from the Phase 1 study of ifabotuzumab in glioblastoma multiforme was presented at the AACR (Free AACR Whitepaper) Annual Meeting 2021.
The CAR-T Phase 1b study results in diffuse large B-cell lymphoma("DLBCL") with lenzilumab were announced, showing 100% Objective Response Rate ("ORR") and no severe cytokine release syndrome or severe neurotoxicity at the recommended dose.
With the positive Phase 1b results, the company terminated its clinical collaboration agreement with Kite, a Gilead Company, and announced plans to initiate a Phase 2 study with all commercially available CD19 CAR-T therapies for DLBCL patients.
Corporate

Dr. Adrian Kilcoyne was appointed to the newly created role of Chief Medical Officer.
Entered into a loan facility with Hercules Capital which will provide the company up to $80 million of secured debt financing.
The company launched a public offering of common stock which closed after quarter-end, resulting in net proceeds to Humanigen of $94.1 million.
Two patents were issued for the use of lenzilumab, expanding the company’s anti-GM-CSF patent portfolio.
Lenzilumab Regulatory Update

The company recently held a meeting with FDA to discuss the filing of an EUA for lenzilumab for hospitalized, hypoxic COVID-19 patients, where topline data from the LIVE-AIR study were reviewed, along with the timeline for submission of additional clinical and manufacturing data for lenzilumab. The company plans to submit an EUA application at the end of May 2021. The company has also been in discussion with the Medicines and Healthcare Products Regulatory Agency ("MHRA") for the use of lenzilumab in COVID-19 patients in the United Kingdom and plans to initiate a rolling CMA submission before the end of the second quarter of 2021. The company also plans to submit for CMA to the European Medicines Agency ("EMA") for the use of lenzilumab in the European Union. Further, the company is reviewing the possibility of similar submissions for approval or compassionate use in other territories or countries worldwide.

The company intends to submit a Biologics License Application ("BLA") to FDA in 2022, for the use of lenzilumab in hospitalized, hypoxic COVID-19 patients. Since BLAs typically require more than one study, the company is currently evaluating the extent to which ACTIV-5/BET-B may serve as a basis for a BLA-confirmatory study for lenzilumab.

First Quarter Ended March 31, 2021 Financial Results

Net loss for the three months ended March 31, 2021 was $65.6 million or $1.25 per share as compared to $2.5 million or $0.11 per share for the three months ended March 31, 2020. The increase in net loss for the first quarter 2021 as compared to the first quarter 2020 was largely due to an increase in total expenses, mainly Research and Development expense ("R&D") of $59.2 million from $0.7 million for the three months ended March 31, 2020 to $59.9 million for the three months ended March 31, 2021. The increase in R&D is primarily due to an increase of $51.4 million of expense in lenzilumab manufacturing costs and $7.5 million for clinical trial expenses related to the LIVE-AIR study, both of which began after the first quarter of 2020. The costs incurred for the production of lenzilumab will continue to be included in R&D until lenzilumab is authorized or approved for commercial use, at which point the amounts expended for production will be classified as inventory.

Cash and Cash Equivalents

Net cash used in operating activities, net of balance sheet changes, was $35.8 million for the three months ended March 31, 2021. During the three months ended March 31, 2021, the company raised net proceeds of $36.1 million from the sale of shares of common stock under its At-the-Market offering program. The company drew the first tranche of $25.0 million under its credit facility with Hercules Capital, providing net proceeds of $24.4 million. As of March 31, 2021, the company had cash and cash equivalents of $92.9 million. The company also completed a public offering in the second quarter of 2021 with net proceeds of $94.1 million. The proforma balance of cash and cash equivalents at March 31, 2021 with the proceeds from the public offering is $187.0 million. The company expects to continue to use its funds on development and manufacturing of lenzilumab in anticipation of its potential commercialization under EUA or other conditional marketing authorizations. In the second quarter of 2021 the company anticipates the amount of spending on lenzilumab production will be at least the same level as the first quarter of 2021. If an EUA or CMA for lenzilumab is not received by mid-2021, the company will seek to decrease or eliminate spending on the production of lenzilumab for commercial use.

On May 13, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported its financial results for the quarter ended March 31, 2021 and provided a business update (Press release, Phio Pharmaceuticals, MAY 13, 2021, View Source [SID1234579938]).

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 year has started out with great momentum across our pipeline, as we continue to present a steady flow of positive data that further demonstrate the value of direct therapy with INTASYL compounds, as well as their application in improving the efficacy of cell-based immunotherapy products. Results from various animal studies, including data presented at the AACR (Free AACR Whitepaper) conference last month, show how INTASYL compounds directly delivered to the tumor can activate the immune response resulting in strong anti-tumor effects. We also presented additional compelling data showing improvements of T cell immunotherapy products by reprogramming them with INTASYL compounds, and their resulting increased in vivo efficacy. For example, at the ASGCT (Free ASGCT Whitepaper) conference this week, we announced data showing how PH-762 can unlock the potential of CAR-T cell therapy in solid tumors. These data provide proof-of-concept for the application of PH-762 mediated PD-1 checkpoint silencing in CAR-T cells prior to adoptive cell therapy to enhance the therapeutic efficacy of CAR-T cell therapy. This is tremendous data for our program, especially when considering a recently published clinical study showing that similar strategies using CRISPR-Cas9 mediated PD-1 disruption in T cells is much less efficient," said Dr. Gerrit Dispersyn, President and CEO of Phio.

"As a result of the overwhelmingly positive data we’ve collected across our pipeline, we have moved to initiate a clinical study using intra-tumoral administration of PH-762 in patients with advanced melanoma, which is expected to begin in the fourth quarter of 2021. The clinical trial will be conducted at the Gustave Roussy Institute, which is one of the leading anti-cancer centers in Europe, with Dr. Caroline Robert as our lead principal investigator. This is an exciting next step in the development of innovative therapeutics based on our INTASYL platform and we look forward to keeping you posted as we move closer towards initiation of the study," concluded Dr. Dispersyn.

Quarter in Review and Recent Corporate Updates

Presented positive data from a study assessing the potential of PH-762, a PD-1 targeting INTASYL compound, to enhance the therapeutic efficacy of HER2-targeted CAR-T cells (HER2CART) in solid tumors, namely a subcutaneous HER2-expressing SKOV3 model of human ovarian cancer in mice. Compared to untreated HER2CART cells, HER2CART cells treated with PH-762 showed a statistically significant and durable inhibition of in vivo tumor growth. These data were included in a poster presentation during the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper).
Announced new in vivo data showing intratumoral (IT) treatment with PD-1 targeting INTASYL (mPH-762) inhibits tumor growth in a dose dependent fashion in both PD-1 responsive and refractory models. These data were included in a poster presentation during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021.
Further bolstered the balance sheet to a total of $32.7 million in cash, following the completion of two financings in Q1 2021 for gross proceeds of $21.7 million in additional capital.
Completed a $7.7 million registered direct offering of common stock priced at-the-market.
Completed a $14.0 million private placement of common stock and warrants priced at-the-market.
Upcoming Pipeline Milestones for 2021

Scheduled to present new in-vivo data regarding dual targeting INTASYL drug therapy (BRD4 and PD-1) at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Initiate a first-in-human clinical study on the use of PH-762 in adoptive cell therapy with tumor infiltrating lymphocytes in patients with metastatic melanoma or squamous cell carcinoma of the head and neck (SSCHN).
Initiate a first-in-human clinical study on the use of PH-762 direct drug therapy (intratumoral injection) in patients with advanced melanoma.
Additional data publications on the Company’s pipeline programs.
Financial Results

Cash Position

At March 31, 2021, the Company had cash of $32.7 million as compared with $14.2 million at December 31, 2020. The Company expects its current cash will be sufficient to fund currently planned operations to the second quarter of 2023.

Research and Development Expenses

Research and development expenses were approximately $2.6 million for the quarter ended March 31, 2021, compared to approximately $1.2 million for the quarter ended March 31, 2020. The increase is primarily due to manufacturing costs and fees for the required preclinical studies in support of the Company’s planned clinical trials for PH-762 as compared to the same period in the prior year.

General and Administrative Expenses

General and administrative expenses were approximately $1.0 million for the quarter ended March 31, 2021, compared to approximately $1.1 million for the quarter ended March 31, 2020. The decrease is primarily due to a decrease in legal fees as compared to the same period in the prior year.

Net Loss

Net loss was $3.4 million, or $0.32 per share, for the quarter ended March 31, 2021, compared with $2.4 million, or $1.33 per share, for the quarter ended March 31, 2020. The increase in net loss was primarily attributable to the increase in research and development expenses, as described above. The change in net loss per share was primarily due to an increase in the number of shares outstanding as a result of the Company’s capital raise activities as compared to the prior year period.