On March 11, 2020 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported an interim clinical data update for cirmtuzumab, a ROR1-targeted monoclonal antibody, combined with ibrutinib, in patients with relapsed/refractory mantle cell lymphoma (MCL) as part of the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial (data cutoff as of March 6, 2020) (Press release, Oncternal Therapeutics, MAR 11, 2020, View Source [SID1234555423]):

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50% Complete Response (CR) rate (6 of 12 evaluable patients), determined by Cheson criteria. One of the six patients had a complete metabolic response (CMR) by PET scan, with a bone marrow biopsy pending. All six CRs are ongoing, including one patient who has remained in CR at over 21 months on study. Four of the six patients achieved CRs within four months on the combination of cirmtuzumab and ibrutinib
33% Partial Response (PR) rate (4 of 12)
17% Stable Disease (SD) rate (2 of 12)
83% best Objective Response (CR or PR) rate (ORR)
100% Clinical Benefit (CR, PR or SD) rate
Median follow-up 6.4 months
Patients had received a median of two prior therapies before participating in this study including chemotherapy; autologous stem cell transplant (SCT); autologous SCT and CAR-T therapy; autologous SCT and allogeneic SCT; and ibrutinib with rituximab
The combination of cirmtuzumab plus ibrutinib has been well tolerated in this study, with adverse events consistent with those reported for ibrutinib alone. There were no dose-limiting toxicities, no discontinuations and no serious adverse events attributed to cirmtuzumab alone.

"The reported complete response rate for patients with MCL treated with cirmtuzumab and ibrutinib is highly encouraging and is higher than previously reported for ibrutinib alone, particularly considering that some of these patients were heavily pre-treated. Patients with relapsed MCL remain in dire need of well-tolerated treatment options that provide deeper and more durable responses," said Hun Ju Lee, M.D., Associate Professor of Medicine in the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center, who is an investigator on the CIRLL clinical trial.

The CIRLL clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM) and is being conducted in collaboration with the University of California San Diego (UC San Diego).

"We are encouraged by the complete response rate for patients with MCL reported in the ongoing CIRLL clinical trial, and look forward to further developing cirmtuzumab in the ongoing clinical trials for patients with MCL, chronic lymphocytic leukemia (CLL) and breast cancer, as well as potentially for other ROR1-expressing solid tumors and hematological malignancies," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the CIRLL Clinical Trial

The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating cirmtuzumab in combination with ibrutinib in separate groups of patients with CLL or MCL. Enrollment of the dose-finding cohorts in CLL and MCL and dose-expansion cohort in CLL has been completed. Enrollment of the dose-expansion cohort in MCL and randomized Phase 2 cohort in CLL is ongoing. Based on the data from the dose-finding cohorts, the recommended dosing regimen was determined to be 600 mg of cirmtuzumab administered intravenously every two weeks for three doses, followed by dosing every four weeks, in combination with 420 mg of ibrutinib administered once daily for patients with CLL, or 560 mg of ibrutinib once daily for patients with MCL, which are the FDA-approved doses of ibrutinib in these indications. Additional information about the CIRM-0001 clinical trial and other clinical trials of cirmtuzumab may be accessed at ClinicalTrials.gov.

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL or MCL, in a collaboration with the UC San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

On March 11, 2020 SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug resistant infections, reported financial results for the year ended December 31, 2019, and provided an update on recent clinical and corporate developments (Press release, Scynexis, MAR 11, 2020, View Source [SID1234555422]).

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"The significant progress made in 2019 advanced us several steps closer to our goal of bringing ibrexafungerp to millions of patients worldwide who are in need of new options to overcome and prevent serious fungal infections. We are conducting multiple late-stage clinical studies of oral ibrexafungerp in indications ranging from vaginal yeast infections, for which there’s only one approved oral therapy, to the life-threatening Candida auris infections affecting patients in hospital settings with compromised immune systems," said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. "Ibrexafungerp represents a novel class of antifungals in a field in which no new class has been approved in nearly 20 years. We believe ibrexafungerp has the potential to become a leading antifungal therapy in both the community and hospital settings, particularly given the lack of innovation in the category, growing resistance to existing treatments, and evolution of new species that pose an urgent threat to the public."

Ibrexafungerp Development Update

Announced positive top-line results for the Phase 3 VANISH-303 study and completion of enrollment in the Phase 3 VANISH-306 study, investigating the safety and efficacy of oral ibrexafungerp as a treatment for women with vaginal yeast infections. In the VANISH-303 study, ibrexafungerp achieved superiority over placebo with high statistical significance (p≤0.001) for the key endpoints required to support the New Drug Application (NDA) filing for this indication. Both the VANISH-303 and VANISH-306 studies achieved faster-than-expected enrollment, demonstrating both the expected market opportunity and SCYNEXIS’s stated timeline to submit an NDA to the U.S. Food and Drug Administration (FDA) for the treatment of VVC in the second half of 2020.

Announced Special Protocol Assessment (SPA) agreement with FDA for Phase 3 CANDLE study, evaluating oral ibrexafungerp for the prevention of recurrent VVC, a condition with no FDA-approved therapies. Enrollment is ongoing in this study and SCYNEXIS anticipates top-line data and supplemental NDA submission in the second half of 2021. An open-label sub-study within CANDLE will also explore ibrexafungerp’s efficacy in patients who failed treatment with fluconazole.

Announced positive results from the second interim analysis of the ongoing Phase 3 open-label FURI study. The study is evaluating oral ibrexafungerp as a salvage treatment in patients with difficult-to-treat mucocutaneous and invasive fungal infections that are refractory to or intolerant of current standards of care, or require a non-azole oral step-down therapy for treatment of azole-resistant Candida species. An independent Data Review Committee assessed the efficacy of oral ibrexafungerp in a second cohort of 21 treated patients from the FURI study. Together with the initial 20 patients reported in January 2019, the dataset consists of 41 patients analyzed to date. Efficacy was consistent across both interim analyses, as oral ibrexafungerp showed clinical benefits in 83% of patients (34 out 41), with 23 patients achieving a complete or partial response and 11 patients a stable disease response. Of the 41 treated patients, only six did not respond to ibrexafungerp treatment and one patient was considered indeterminate. The data will be presented at an upcoming scientific conference in the first half of 2020.

Amended the protocol for the ongoing Phase 3 open-label FURI study. Under the amended study design, the protocol was expanded to include patients with complex fungal infections such as aspergillosis, coccidioidomycosis, histoplasmosis, blastomycosis and infections caused by other emerging fungi including yeasts and molds in addition to Candida infections. Maximum allowed treatment duration with ibrexafungerp has been extended from 90 days to up to 180 days, as needed for chronic conditions. Ibrexafungerp will also be available as a combination therapy with standard of care (SoC) for certain infections.

Enrollment ongoing in Phase 3 open-label CARES study. Enrollment continues in the CARES study for patients with Candida auris infections. The Centers for Disease Control and Prevention (CDC) recently declared Candida auris, an emerging, multidrug-resistant pathogen, an "Urgent Threat" to public health.

Enrollment ongoing in Phase 2 SCYNERGIA study. Enrollment continues in the SCYNERGIA study for patients with invasive aspergillosis (IA) and SCYNEXIS recently amended the protocol to include transplanted patients, who are a well-known category at risk of fatal infection due to Aspergillus.

SCYNEXIS continues to explore development of IV formulation of ibrexafungerp. While oral ibrexafungerp is progressing as a potentially valuable option to treat hospital-based invasive fungal infections, as recently shown in the second interim analysis from the FURI study, SCYNEXIS is developing an intravenous liposomal formulation of ibrexafungerp and will provide further updates on this program in the future.

SCYNEXIS continues to educate the scientific community about the broad clinical utility of ibrexafungerp. SCYNEXIS attended 11 national and international scientific conferences with 30 oral and poster presentations. In 2019, a total of ten ibrexafungerp scientific publications were released.
Corporate Highlights

In December 2019, SCYNEXIS raised approximately $35 million in a public offering of common stock and warrants. SCYNEXIS sold 38,888,889 shares of its common stock and warrants to purchase up to 38,888,889 shares of SCYNEXIS’s common stock. Additionally, the underwriters exercised an option to purchase 5,833,333 additional warrants. Based upon SCYNEXIS’s existing operating plan, SCYNEXIS believes that its existing cash and cash equivalents and short-term investments, and the sale of a portion of SCYNEXIS’s NOLs, will enable it to fund operating requirements past a potential Prescription Drug User Fee Act (PDUFA) date in mid-2021 for the treatment of VVC when SCYNEXIS expects the FDA to complete the review of the NDA and potentially approve ibrexafungerp for the treatment of VVC.

In January 2020, SCYNEXIS entered into an agreement to sell a portion of its unused Net Operating Losses (NOLs) and R&D credits; SCYNEXIS expects to receive a cash receipt of approximately $3.1 million.

In December 2019, SCYNEXIS appointed Philippe Tinmouth to its Board of Directors. Mr. Tinmouth brings over 20 years of experience across multiple business development and alliance management roles.
Full Year 2019 Financial Results
Cash, cash equivalents and short-term investments totaled $48.4 million as of December 31, 2019, compared to $44.2 million in cash, cash equivalents, and short-term investments at December 31, 2018.

Research and development expenses for the year ended December 31, 2019 increased to $38.4 million from $21.6 million for the year ended December 31, 2018. The increase of $16.8 million, or 78.1%, was primarily driven by a milestone payment made in 2019 to Merck upon initiation of the Phase 3 VVC registration study, an increase of $11.8 million in clinical development expenses, an increase of $0.6 million in chemistry, manufacturing, and controls (CMC), and an increase of $1.1 million in salary and personnel related costs, and a net increase of $1.0 million in other research and development expenses, offset in part by a decrease of $1.7 million in preclinical expenses.

Selling, general and administrative expenses for the year ended December 31, 2019 increased to $10.6 million from $8.7 million for the year ended December 31, 2018. The increase of $2.0 million, or 22.7%, was primarily driven by a $1.0 million increase in business development and commercial related costs, a $0.6 million increase in professional fees, a $0.4 million increase in salary and personnel related costs, and a net increase in other selling, general and administrative expenses of $0.2 million, offset in part by a $0.2 million charge for deferred offering costs recognized in 2018.

Total other expense was $4.8 million for the year ended December 31, 2019, compared to total other income of $10.8 million for the year ended December 31, 2018. The $4.8 million in total other expense is primarily attributable to a $4.5 million non-cash loss and a $1.6 million non-cash gain recorded on the fair value adjustments of the warrant liabilities and derivative liability, respectively, for the year ended December 31, 2019.

Net loss for the year ended December 31, 2019 was $53.7 million, or ($0.96) per basic and diluted share, compared to a net loss of $12.5 million, or ($0.28) per basic and diluted share, for the year ended December 31, 2018.

About Ibrexafungerp
Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an investigational antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors called triterpenoids. This agent combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and IV formulations. Ibrexafungerp is currently in development for the treatment of fungal infections caused primarily by Candida (including C. auris) and Aspergillus species. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains. The FDA has granted Qualified Infectious Disease Product (QIDP) and Fast Track designations for the formulations of ibrexafungerp for the indications of invasive candidiasis (IC) (including candidemia), invasive aspergillosis (IA) and vulvovaginal candidiasis (VVC) and has granted Orphan Drug Designation for the IC and IA indications. Ibrexafungerp is formerly known as SCY-078.

On March 11, 2020 Synlogic (Nasdaq: SYBX) reported that Richard Riese, M.D., Ph.D., Synlogic’s chief medical officer, will present at the Chardan Microbiome Medicines Summit at Noon ET on Monday, March 16th, 2020 (Press release, Synlogic, MAR 11, 2020, View Source [SID1234555421]).

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This is a virtual event. A live webcast of the presentation can be accessed under "Event Calendar" in the Investors & Media section of the Company’s website. An archived copy of the webcast will be available on the Synlogic website for approximately 30 days after the event.

On March 11, 2020 Pfenex Inc. (NYSE American: PFNX) reported that development and licensing biotechnology company focused on leveraging its Pfēnex Expression Technology to develop and improve protein therapies for unmet patient needs (Press release, Pfenex, MAR 11, 2020, View Source [SID1234555420]). Using the patented Pfēnex Expression Technology platform, the Company has developed the FDA-approved PF708 product indicated for the treatment of osteoporosis in certain patients at high risk for fracture and created an advanced pipeline of therapeutic equivalents, biologics and vaccines in various stages of development. Today Pfenex Inc. reported financial results for the fourth quarter and year ended December 31, 2019 and provided a business update.

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"This is an exciting time for our company as we continue to advance towards the U.S. launch of our first U.S. Food and Drug Administration (FDA) approved product, PF708. Over the past several months, Alvogen, our partner to which we have transferred the approved PF708 NDA, has worked towards establishing manufacturing, distribution, sales and marketing of PF708, and is preparing for the product’s launch. Alvogen has indicated that it intends to launch the FDA-approved PF708 product in the U.S. upon an FDA decision on the therapeutic equivalence evaluation of the product to Forteo (teriparatide injection), which could permit PF708 to be automatically substituted for Forteo in many states. In October, we submitted a comparative use human factor study report to the FDA as part of the package supporting a determination that the products are therapeutically equivalent. We believe this submission completes the information package required by the FDA to make its decision on the "A" rating," stated Eef Schimmelpennink, Chief Executive Officer of Pfenex.

"This past year was a transformational period for Pfenex. We moved towards being a business with an FDA approved product nearing commercialization, and we generated milestone revenue with certain of our development products. We have also been moving to expand our pipeline through the use of our patented Pfēnex Expression Technology platform. The Pfenex team has executed on our strategy and as a result, in both the fourth quarter and throughout 2019, we have achieved a number of milestones that resulted in payments from our collaboration partners for each of our three lead programs for an aggregate total of $31.1 million in milestone payments for 2019. This revenue has allowed us to invest in the advancement of PF708 and our broader portfolio of products, and to evaluate the development of new programs through our platform which we believe may help deliver long-term value to our shareholders," stated Mr. Schimmelpennink.

Business Review and Update

FDA-approved PF708 product and proposed therapeutic equivalent to Forteo

During the fourth quarter of 2019, the FDA approved the new drug application (NDA) for PF708 submitted under the 505(b)(2) regulatory pathway, with Forteo (teriparatide injection) as the reference drug. Like Forteo, the FDA-approved PF708 product is indicated for the treatment of osteoporosis in certain patients at high risk of fracture.

In advance of a potential commercial launch in the U.S., Pfenex and Alvogen, the Company’s U.S commercial partner, are in the process of seeking FDA designation of PF708 as therapeutically equivalent to Forteo, which, if achieved, would permit PF708 to be automatically substituted for Forteo in many states. The therapeutic equivalence rating for this product will be primarily based on the FDA evaluating three distinct requirements that center around showing pharmaceutical equivalence, bioequivalence and human factors comparability. The Company provided pharmaceutical equivalence and bioequivalence data as part of the NDA for PF708. In the fourth quarter of 2019, Pfenex submitted to the FDA a comparative use human factors (HF) study report, as requested by the FDA, which we believe provides support for an "A" rating. The HF study found that the user interface of the PF708 product was noninferior to that of Forteo for each critical user task evaluated in the study. Pfenex believes this completes the information package required by the FDA to evaluate the therapeutic equivalence of PF708. If PF708 is designated as therapeutically equivalent to Forteo, Pfenex will be eligible to receive up to an additional $20 million in support and regulatory milestone payments from Alvogen, and may also be eligible to receive from Alvogen a 50% gross profit split on sales.

If rated differently, the Company will be eligible to receive from Alvogen up to a 40% gross profit split on sales. In anticipation of the U.S. launch, Pfenex and Alvogen are preparing commercial manufacturing, supply chain, and commercialization activities for PF708. Alvogen is a global pharmaceutical company with a track record of developing, manufacturing and selling generic, brand, over-the-counter brands (OTC) and biosimilar products for patients around the world.

Alvogen, which also has exclusive development and commercialization rights for PF708 in the European Union (EU), Middle East and North Africa (MENA) and the Rest-of-World territories (except those licensed to NT Pharma), currently has exclusive commercialization agreements for PF708 with Theramex in Europe and Switzerland, PharmBio Korea in South Korea, JAMP Pharma in Canada, and Kamada Ltd. in Israel. In the EU, the accepted Marketing Authorization Application (MAA) for PF708 is under review by the European Medicines Agency (EMA) and continues to make progress. Pfenex believes PF708 could receive regulatory approval as early as the second half of 2020, subject to granting of a marketing authorization by the European Commission under the EU centralized procedure and other factors. If approved, PF708 would receive marketing authorization in all member states of the EU, as well as in Iceland, Liechtenstein and Norway and be commercialized by Alvogen’s partner Theramex. The MAA for PF708 was submitted by Alvogen to the EMA as a biosimilar to Forsteo, which achieved $253 million sales in the E.U. in 2019.

During the fourth quarter of 2019, Alvogen submitted a Marketing Authorization Application to the Kingdom of Saudi Arabia’s Saudi FDA, and entered into exclusive commercialization agreements for PF708 with PharmBio Korea in South Korea and JAMP Pharma in Canada. Under the terms of these agreements, Alvogen will be responsible for the local activities through PharmBio and JAMP Pharma. Alvogen is currently working on licensing agreements for additional territories.

In addition, Pfenex has granted an exclusive license to NT Pharma to commercialize PF708 in Mainland China, Hong Kong, Singapore, Malaysia and Thailand and a non-exclusive license to conduct development activities in such territories with respect to PF708.

Pfenex believes PF708 has the potential to enhance patient access to an important therapy as a cost-effective alternative to Forteo, which had $1.4 billion in global sales in 2019. In October, upon U.S. FDA approval of PF708, Pfenex earned a $2.5 million milestone payment from Alvogen and recognized an additional $2.5 million in revenue for the upfront payment from Alvogen that had been previously deferred. The Company may also be eligible to earn up to a $20 million milestone payment if the FDA grants an "A" therapeutic equivalence rating to PF708.

Jazz Collaboration Agreement

Pfenex announced in the fourth quarter of 2019 that it earned a $15 million development milestone payment under its development and license agreement with Jazz Pharmaceuticals plc (Jazz). The milestone is associated with process development activities for PF745 (JZP-341), a long-acting recombinant Erwinia asparaginase. Jazz announced in December 2019 that the first patient was enrolled in a pivotal Phase 2/3 clinical study for PF743 (JZP-458), a recombinant Erwinia asparaginase. Jazz has reported that the study is expected to enroll approximately 100 patients with a planned interim analysis at approximately 50 patients. Jazz has indicated that enrollment for the study is expected to be completed by the fourth quarter 2020. Jazz has received fast track designation for PF743, and recently stated that it anticipates filing the BLA as early as the Q4 of this year. This study is being conducted in collaboration with Children’s Oncology Group.

Under the terms of the development and license agreement, Pfenex is eligible to receive an aggregate total of up to $224.5 million in development and sales milestone fees, of which $162.5 million is still eligible to be received by Pfenex. This includes up to $3.5 million for development milestones, $34 million in regulatory milestones and $125 million in sales milestones. Pfenex may also be eligible to receive tiered mid-single digit royalties based on worldwide sales of any products resulting from the collaboration.

CRM197

CRM197 is a non-toxic mutant of diphtheria toxin. It is a well characterized protein and functions as a carrier for polysaccharides and haptens, making them immunogenic. CRM197 is currently being used by Pfenex’s vaccine development focused pharmaceutical partners, including in multiple Phase 3 clinical studies by Merck & Co., Inc. (Merck) and the Serum Institute of India Private Ltd. (SIIPL) for such diseases as pneumococcal and meningitis bacterial infections.

Merck is using Pfenex’s CRM197 in its vaccines including PCV-15 (V114), an investigational 15-valent polyvalent conjugate vaccine for the prevention of pneumococcal disease, currently in 15 Phase 3 studies. If approved, V114 is expected to be positioned as a key product in the pneumococcal vaccine market.

SIIPL is using Pfenex’s CRM197 in multiple programs. SIIPL has developed a 10-valent pneumococcal conjugate vaccine, Pneumosil, which utilizes our CRM197, and initiated the process of World Health Organization prequalification for Pneumosil in the first quarter of 2019. SIIPL achieved WHO prequalification for their product in the fourth quarter of 2019 and is preparing to make the product available for procurement by United Nations agencies and the GAVI vaccine alliance. They are also completing a phase 3 clinical trial that will support a regulatory submission in India. Pfenex is eligible to receive a tiered royalty payment based upon net sales for both products, subject to regulatory approval.

Arcellx – sparX Protein Development Agreement

In August 2019, Pfenex announced its development, evaluation and license agreement with Arcellx which provides access to the Pfēnex Expression Technology platform to advance Arcellx’s proprietary sparX proteins that activate, silence and reprogram antigen-receptor complex T cell-based therapies. Under the terms of the agreement, Pfenex is eligible to receive development funding in addition to development, regulatory and commercial milestones ranging from $2.6 million to $18 million for each product incorporating a sparX protein expressed using the Pfēnex Expression Technology, as well as royalties on worldwide sales of any such products. Pfenex has completed the development of both sparX 1 (PF753) and sparX 2 (PF754), and Arcellx has opted in to the commercial license for both production strains. Pfenex looks forward to providing updates on this collaboration.

Financial Highlights for the Fourth Quarter and Full Year 2019

Total Revenue increased by $21.0 million, or 628%, to $24.4 million in the three-month period ended December 31, 2019, compared to $3.4 million in the same period in 2018. The increase in revenue for the quarter was primarily due to a $15 million development milestone achieved during the quarter related to the Jazz collaboration agreement, $5.0 million earned from Alvogen for FDA approval of our NDA for PF708, and increased product sales of CRM197. For the full year, revenue increased by $35.4 million, or 239%, from $14.9 million in 2018 to $50.3 million in 2019. The increase in revenue primarily resulted from $26 million in development milestones achieved from the collaboration agreement with Jazz, Alvogen milestone and sublicensing revenue of $11 million, and revenue from Arcellx and CRM197 product sales. The increase was partially offset by a decrease in revenue from BARDA and recognized revenue from Jazz that was previously deferred, as the upfront payment from Jazz was fully amortized in mid-2019.

Cost of Revenue was static at $1.1 million for both the three-month periods ended December 31, 2019 and 2018. Decreases resulting from reduced activity from the BARDA program were offset by increases from CRM197 product sales. For the full year, cost of revenue decreased by $0.1 million, or 3%, to $4.9 million in 2019 compared to $5.0 million in 2018. The change was driven by a decline in BARDA activity, offset by increases resulting from work on Arcellx, as well as greater CRM197 product sales.

Research and development expenses increased by approximately $0.6 million, or 12%, to $5.9 million in the three-month period ended December 31, 2019, compared to $5.3 million in same period in 2018. The increase was primarily due to new research projects, partially offset by a decrease in costs related to PF708, as the majority of the work performed to support the NDA filing was completed in late 2018. For the full year, research and development expenses decreased by approximately $8.4 million, or 25%, to $25.5 million in 2019 compared to $33.9 million in 2018. The decrease was chiefly due to the reduction of labor and subcontractor costs, as the majority of the work performed to support the PF708 NDA filing was completed in late 2018.

Selling, general and administrative expenses increased by approximately $1.9 million, or 50%, to $5.9 million in the three-month period ended December 31, 2019, compared to $3.9 million in the same period in 2018. The increases were primarily due to higher expenses related to legal and consulting fees, employee costs and the expansion of business development efforts. For the full year, selling, general and administrative expenses increased by $3.3 million, or 21%, to $19.1 million in 2019 compared to $15.8 million in 2018. The increase was primarily driven by higher legal and audit fees, employee costs and the expansion of business development efforts.

Cash and cash equivalents as of December 31, 2019, were $55.6 million. In addition, in two separate transactions in the first months of 2020, Pfenex utilized its ATM facility to place approximately 1.8 million shares for approximate net proceeds of $19.4 million. Pfenex believes that its existing cash and cash equivalents and cash inflow from operations will be sufficient to meet Pfenex’s anticipated cash needs for at least the next 12 months.

Conference Call Information

The Pfenex management will host a conference call and webcast today at 4:30 PM Eastern Time. Participants may access the call by dialing 866-376-8058 (Domestic) or 412-542-4131 (International). The call will also be webcast and can be accessed from the Investors section of the Company’s website at www.pfenex.com or View Source

A replay of the call will also be available through March 18th. Participants may access the replay of the call by dialing 877-344-7529 (Domestic) or 412-317-0088 (International) and providing the conference ID number: 10139830.

About PF708

PF708 was approved in the U.S. under the 505(b)(2) regulatory pathway, with Forteo (teriparatide injection) as the reference drug. The FDA-approved PF708 product is indicated for the treatment of osteoporosis in certain patients at high risk for fracture. Pursuant to the Development and License Agreement with Alvogen, Alvogen is responsible for commercializing and manufacturing PF708 in the U.S. and for fulfilling all regulatory requirements associated with maintaining the PF708 NDA. Alvogen also has exclusive rights to commercialize and manufacture PF708 in the EU, certain countries in the Middle East and North Africa (MENA), and the Rest of World (ROW) territories (the latter defined as all countries outside of the EU, U.S. and MENA, excluding Mainland China, Hong Kong, Singapore, Malaysia and Thailand). A marketing authorization application for PF708 has been filed and accepted with the EMA using the biosimilar pathway with Forsteo as the reference medicinal product and has been filed with the Kingdom of Saudi Arabia’s Saudi Food and Drug Authority (SFDA). Pursuant to the Development and License Agreement with NT Pharma Group Company Ltd. (NT Pharma), we granted an exclusive license to NT Pharma to commercialize PF708 in Mainland China, Hong Kong, Singapore, Malaysia and Thailand and a non-exclusive license to conduct development activities in such territories with respect to PF708. Forteo and Forsteo are approved and marketed by Eli Lilly companies for the treatment of osteoporosis in certain patients with a high risk of fracture. Forteo and Forsteo achieved $1.4 billion in global product sales in 2019.

On March 11, 2020 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported its financial results for the fourth quarter and full year ended December 31, 2019 (Press release, Navidea Biopharmaceuticals, MAR 11, 2020, View Source [SID1234555419]).

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"During the fourth quarter, Navidea made great strides in its enrollment of the NAV 3-31 Phase 2B trial in patients with rheumatoid arthritis," said Mr. Jed A. Latkin, Chief Executive Officer of Navidea. "The Company continued its dialogue with several key potential partners and we anticipate providing updates on those initiatives in the very near future. Furthermore, with the most recent financing, the Company put in place the steps necessary to launch the next critical trials."

Fourth Quarter 2019 Highlights and Subsequent Events

Continued with double-digit subject enrollment in the Company’s NAV3-31 Phase 2b study in rheumatoid arthritis ("RA") and completed enrollment of subjects in Arms 1 and 2.

Announced positive results of the first interim analysis of the NAV3-31 Phase 2b study, demonstrating that Tc99m tilmanocept imaging can provide robust, quantitative imaging in healthy controls and in patients with active RA, and that this imaging is stable, reproducible, and can define joints with and without RA-involved inflammation.

Completed enrollment in NAV3-24, a Phase 1 Kaposi’s Sarcoma trial; All imaging has been completed and the Company is currently compiling results.

Continued enrollment in the Investigator Initiated Phase 2 trial being run at the Massachusetts General Hospital evaluating Tc99m tilmanocept uptake in atherosclerotic plaques of HIV-infected individuals.

Entered into a collaboration agreement with IMV Inc., a clinical-stage immuno-oncology company, to explore the combinatory effect of Navidea’s and IMV’s proprietary immuno-oncology platforms.

Converted the Tilmanocept Uptake Value quantitative imaging analysis provisional patent to an A1 patent application, and filed an additional provisional patent relevant to both imaging and therapeutic applications.

Executed agreements with five investors, including an existing investor, to purchase approximately 2.1 million shares of the Company’s common stock in a private placement for aggregate gross proceeds to Navidea of approximately $1.9 million.

Won summary judgment in the Court of Common Pleas for Franklin County, Ohio (the "Ohio Court") related to the Company’s ongoing litigation with Capital Royalty Partners II, L.P., et al ("CRG"), in the amount of $4.3 million plus interest (the "Judgment"). The Ohio Court also found that there was no unjust enrichment or conversion by CRG. The decision is a final appealable order and terminated the case.

Executed a binding term sheet to sell the Judgment for $4.2 million of proceeds to Navidea.

Executed agreements with two existing investors to purchase approximately 4.0 million shares of the Company’s common stock for aggregate gross proceeds to Navidea of approximately $3.4 million.

Following the funding transactions described above, the Company regained compliance with the NYSE American’s continued listing standards with stockholders’ equity of $6.0 million.

Michael Rosol, Ph.D., Chief Medical Officer for Navidea, said, "The clinical research team has been working diligently to advance the technology in key disease areas, with an emphasis on our ongoing RA trials. We continue to advance our Phase 2B trial in RA, building upon last quarter’s announced interim analysis results, and with an eye towards the second interim analysis. We are also planning for the start of our second Phase 2B trial comparing tilmanocept imaging to synovial tissue biopsy samples of RA patients as well as the Phase 3 trial."

Financial Results

Navidea’s consolidated balance sheets, statements of operations, and statements of stockholders’ equity have been restated, as required, for all periods presented to reflect the April 2019 reverse stock split as if it had occurred on January 1, 2018. The consolidated statements of cash flows were not impacted by the reverse stock split.

Total revenues for the fourth quarters of both 2018 and 2019 were $119,000. Total revenues for fiscal 2019 were $658,000, compared to $1.2 million in 2018. The year-to-year decrease was primarily due to a decrease in license revenue related to the sublicense of the Company’s NAV4694 technology, which included a non-refundable upfront payment in 2018, coupled with a reduction in grant revenue related to Small Business Innovation Research grants from the National Institutes of Health supporting Manocept development.

Research and development ("R&D") expenses for the fourth quarter of 2019 were $1.7 million, compared to $854,000 in the same period of 2018. R&D expenses in 2019 were $5.3 million, compared to $4.2 million in 2018. The increase was primarily due to net increases in drug project expenses, which includes Manocept diagnostic and Tc99m tilmanocept development costs, offset by decreased Manocept therapeutic and NAV4694 development costs.

Selling, general and administrative ("SG&A") expenses for the fourth quarter of 2019 were $1.2 million, compared to $1.4 million in the same period of 2018. SG&A expenses for 2019 were $6.3 million, compared to $7.7 million in 2018. The decrease was primarily related to the resignation of the Company’s former CEO in 2018, coupled with net decreases in salaries and bonuses, investor relations, general office expenses and taxes, offset by increased legal and professional services, primarily related to litigation with the Company’s former CEO.

Navidea’s net loss attributable to common stockholders for the fourth quarter of 2019 was $2.8 million, or $0.15 per share, compared to a net loss attributable to common stockholders of $3.2 million, or $0.33 per share, for the same period in 2018. Navidea’s net loss attributable to common stockholders for 2019 was $10.9 million, or $0.76 per share, compared to a net loss attributable to common stockholders of $16.1 million, or $1.89 per share, for 2018.

Navidea ended the fourth quarter of 2019 with $1.0 million in cash and investments. Per Navidea’s recent filings with the SEC, the Company executed funding transactions totaling $7.6 million in proceeds during the first quarter of 2020.

Conference Call Details

Investors and the public are invited to dial into the earnings call through the information listed below, or participate via the audio webcast on the company website. Participants who would like to ask questions during the question and answer session will be prompted by the moderator, who will provide instructions.

Event:

Q4 2019 Earnings and Business Update Conference Call

Date:

Wednesday, March 11, 2020

Time:

5:00 p.m. (EDT)

U.S. & Canada Dial-in:

877-407-0312

International Dial-in:

+1 201-389-0899

Conference ID:

13699935

Webcast Link: View Source

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website