On March 16, 2022 Transgene (Euronext Paris: TNG) (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported its financial results for 2021 and provides an update on its product pipeline (Press release, Transgene, MAR 16, 2022, View Source [SID1234610180]).

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Hedi Ben Brahim, CEO of Transgene commented: "It has been more than a year since I joined Transgene as Chairman and Chief Executive Officer and I am pleased and proud to have experienced and delivered such a successful year for the Company.
Transgene achieved several important milestones in 2021. We announced the first positive data from two Phase I trials with TG4050, our individualized therapeutic vaccine based on our myvac platform. These results demonstrated the immunogenicity of the vaccine, which led to the first signs of clinical activity. We expect to confirm these results in the coming months and to provide more in-depth data at major scientific congresses in 2022.
The Phase II trial with TG4001, our therapeutic vaccine against HPV16-positive anogenital cancers, was launched in 2021, with the first patient enrolled in June; recruitment is continuing at a steady pace. First data from an interim analysis, including up to 50 patients, is anticipated in the fourth quarter of 2022.
We also made significant progress with our oncolytic virus pipeline. We recruited the first patient into the Phase I/IIa study evaluating BT-001, our first candidate from our Invir.IO platform. We also presented the first Phase I data with TG6002 at two major conferences in 2021: AACR (Free AACR Whitepaper) and ESMO (Free ESMO Whitepaper). These results confirm the feasibility of intravenous administration of this oncolytic virus. The ability to be given intravenously would considerably extend the use of our Invir.IO based virus therapies in oncology, significantly expanding the market opportunity they can address.
In addition, our expertise and the clear benefits that our Invir.IO platform can deliver was recognized with the first license option exercised by AstraZeneca for an oncolytic virus in late 2021. This exercise results in an upfront payment of $8 million. The collaboration with AstraZeneca continues under the agreement for the development of other oncolytic immunotherapies by Transgene.
Following the successful completion of a €34.1 million private placement in June 2021 and the additional sale of Tasly BioPharmaceuticals shares in September 2021 for €17.4 million, Transgene has financial visibility until the end of 2023. This puts us in strong position to pursue Transgene’s mission: create value by developing new innovative cancer therapies."

PRELIMINARY POSITIVE RESULTS WITH TG4050 CONFIRMING ITS POTENTIAL AND REINFORCING TRANSGENE’S POSITION AS A GLOBAL LEADER IN THE FIELD OF INDIVIDUALIZED THERAPEUTIC CANCER VACCINES

Transgene is developing TG4050, an individualized immunotherapy against cancer based on its highly innovative myvac platform. This platform delivers a customized approach, by combining Transgene’s expertise in viral engineering with NEC’s artificial intelligence capabilities. TG4050 is currently being assessed in two Phase I clinical trials in Europe and in the US (in ovarian and HPV-negative head and neck cancers); NEC is financing 50% of these studies. The product is manufactured by Transgene in an in-house GMP production unit in Strasbourg. The first results were announced in November 2021.

Positive data were generated in the first six patients treated and demonstrate the strong potential of TG4050. The specific immune responses observed show a robust T-cell response against multiple targeted mutations (neoantigens), with a median of 10 positive responses per patient. The development of adaptive responses also suggest that the vaccine is able to effectively prime the immune system. The studies also provide preliminary data on the clinical activity of this individualized immunotherapy. Four patients were treated in the ovarian cancer study, including one patient with a CA-125 elevation which was cleared by vaccination for nine months before death from an unrelated chronic disease, and one patient who remained stable for nine months after the appearance of radiological lesions and initiation of treatment. In the head and neck cancer study, patients treated for 10 and 5 months, respectively, were stable and disease-free as of November 22, 2021. More details are available here.

These data reinforce the rationale for TG4050’s prediction system and support the validation of the myvac platform as an efficient approach for anti-tumor vaccination. Additional data will be presented at the AACR (Free AACR Whitepaper) annual meeting on April 12, 2022, and at other scientific conferences in 2022.

ONGOING ENROLLMENT IN THE RANDOMIZED PHASE II STUDY WITH TG4001 IN HPV16-POSITIVE ANOGENITAL CANCERS

TG4001 is a therapeutic vaccine targeting HPV-positive tumors, and is engineered to express HPV16 E6 and E7 antigens and interleukin 2 (IL-2) which stimulates immune responses. TG4001 is being developed to target recurrent or metastatic HPV-16 positive cancers, without liver metastasis, based on a clinical benefit observed in the Phase Ib/II trial. TG4001 is currently being evaluated in a randomized Phase II trial of up to 150 patients comparing the efficacy of the combination of TG4001 with avelumab versus avelumab alone. The first patient was enrolled in June 2021. The trial is actively enrolling patients in Europe (France and Spain) and has recently been initiated in the US.

An interim analysis will be performed after the inclusion of approximately 50 patients. Transgene expects to report the results of this analysis in the fourth quarter of 2022.

BT-001, FIRST ONCOLYTIC VIRUS BASED ON INVIR.IO PLATFORM, CONTINUES ITS CLINICAL DEVELOPMENT IN EUROPE AND IN THE US

BT-001 is a patented VVcopTK-RR- oncolytic virus, with high antitumor potential, based on the Invir.IO platform. It is being co-developed with BioInvent. It has been engineered to express both a human recombinant anti-CTLA-4 antibody and the human GM-CSF cytokine locally in the tumor, aiming at inducing a local Treg depletion, and providing significant therapeutic activity by limiting systemic exposure.

Promising preclinical results with BT-001 were presented at the SITC (Free SITC Whitepaper) 2021 annual meetings. They demonstrated high and robust intratumoral antitumor activity, resulting in tumor disappearance in in vivo models. In January 2022, preclinical proof-of-concept data were published in the Journal for ImmunoTherapy of Cancer (JITC). The published results demonstrated the potential of the virus to provide therapeutic benefit beyond current anti-PD1/anti-CTLA-4 immune checkpoint inhibitors. The article can be downloaded here.
Further preclinical data will be presented at the AACR (Free AACR Whitepaper) on April 12, 2022.

A multicenter, open-label Phase I/IIa study is evaluating ascending doses of BT-001 alone and in combination with pembrolizumab. The first patient in this trial, approved in Europe (France and Belgium) and in the US, was enrolled in February 2021. Patient recruitment is progressing as expected.

The next clinical update on the ongoing Phase I trial is expected in the second quarter of 2022.

TG6002 PROVIDES THE CLINICAL PROOF-OF-CONCEPT OF THE INTRAVENOUS ADMINISTRATION OF TRANSGENE’S ONCOLYTIC VIRUSES

TG6002 is based on Transgene’s patented VVcopTK-RR- strain, it has been engineered to express a chemotherapeutic agent (5-FU) directly in the tumor. TG6002 is being assessed in two Phase I/II clinical trials in gastrointestinal cancers, for which 5-FU is a common treatment. Its administration is evaluated by the intravenous and intrahepatic artery routes.

Initial Phase I data were presented at AACR (Free AACR Whitepaper) 2021 and ESMO (Free ESMO Whitepaper) 2021. The Phase I data provide the clinical proof-of-concept of the feasibility of the intravenous (IV) administration of Transgene’s patented oncolytic virus backbone. The data showed that, after IV administration, TG6002 is able to selectively replicate and persist in tumor cells leading to the local expression of its functional payload (the FCU1 gene).

This finding supports the potential of IV administration of oncolytic virus based on the VVcopTK-RR- strain behind the Invir.IO platform, extending the use of Transgene’s oncolytic therapies to a broad range of solid tumors.

The Phase I trial evaluating TG6002 administered intravenously is expected to be completed by mid-2022. Comprehensive translational data will be presented in the fourth quarter of 2022.

SUMMARY OF ONGOING CLINICAL TRIALS

myvac

TG4050

Phase I

NCT03839524

Targets: tumor neoantigens

Codeveloped with NEC
First positive data in first 6 patients demonstrating the immunogenicity of the vaccine as well as first signs of clinical activity
Ovarian cancer – after surgery and first-line chemotherapy

Trial ongoing in the US and in France
First patient treated in 2020 – patient enrollment progressing in line with forecast
> Additional data expected in 2022, including at the AACR (Free AACR Whitepaper)

TG4050

Phase I

NCT04183166

HPV-negative head and neck cancer – after surgery and adjuvant therapy

Trial ongoing in the UK and in France
First patient treated in Jan. 2021 – patient enrollment progressing in line with forecast
> Additional data expected in 2022, including at the AACR (Free AACR Whitepaper)

TG4001

+ avelumab
Phase II

NCT03260023

Targets: HPV16 E6 and E7 oncoproteins

Recurrent/metastatic anogenital HPV-positive – 1st (patients ineligible for chemotherapy) and 2nd line

Randomized Phase II trial comparing the combination of TG4001 with avelumab versus avelumab alone
First patient treated in June 2021. Active patient enrollment in Europe (France and Spain), trial initiation in the US
> Results of the interim analysis expected in Q4 2022 (N≈50)

Invir.IO

BT-001

Phase I/IIa

NCT04725331

Payload: anti-CTLA4 antibody and GM-CSF cytokine

Solid tumors

Co-development with BioInvent
Very encouraging preclinical results presented at SITC (Free SITC Whitepaper) 2021 and soon at AACR (Free AACR Whitepaper) 2022
Trial ongoing in France, Belgium and recently approved in the US. First patient included in February 2021
> Next clinical update expected in Q2 2022

TG6002

Phase I/IIa

NCT03724071

Payload: FCU1 for the local production of a 5-FU chemotherapy

Gastro-intestinal cancer (colorectal cancer for Phase II) – Intravenous (IV) administration

Multicenter trial ongoing in Belgium, France and Spain
Proof-of-concept data of the intravenous administration presented at the AACR (Free AACR Whitepaper) 2021 and ESMO (Free ESMO Whitepaper) 2021
Dose escalation completed to the maximum projected dose (3*109 pfu), confirming the good safety profile. Ongoing dose escalation (109 and 3*109 pfu)
> End of Phase I expected mid-2022

TG6002

Phase I/IIa

NCT04194034

Colorectal cancer with liver metastasis – Intrahepatic artery (IHA) administration

Multicenter trial ongoing in the UK and in France
Ongoing enrollment of patients from the latest dose escalation cohort (109 pfu)
> First data expected mid-2022

ASTRAZENECA COLLABORATION : NEW MILESTONE
WITH THE FIRST LICENSE OPTION EXERCISE

AstraZeneca has exercised a first license option in December 2021 for an oncolytic virus from Transgene’s Invir.IO platform. Transgene received an $8 million payment for the exercise of this option and is also eligible to receive development, regulatory and sales-based milestones payments as well as a royalty based on future commercial sales.
The collaboration with AstraZeneca, which includes co-development of other potential oncolytic immunotherapies, is ongoing. AstraZeneca has an option to acquire the rights to each of these innovative drug candidates for further clinical development.

A NEW COLLABORATION WITH INVIR.IO PLATFORM

In January 2022, Transgene announced the launch of a preclinical collaboration with PersonGen BioTherapeutics. This collaboration aims to evaluate the feasibility and efficacy of a combination therapy against solid tumors, combining PersonGen’s CAR T cell injection with an oncolytic virus from the Invir.IO platform.

APPOINTMENT OF STEVEN BLOOM
AS CHIEF BUSINESS OFFICER

Steven Bloom joined Transgene as Vice President, Chief Business Officer (CBO) in February 2022. He joined Transgene’s executive committee to lead global business development strategy, alliance management and program management of the Company, with a focus on building a strong visibility in the US as part of establishing Transgene as a world leader in virus-based immunotherapies.

KEY FINANCIALS FOR 2021

– Operating income of €17.4 million in 2021, compared to €9.9 million in 2020.
R&D services for third parties amounted to €10.0 million in 2021 (€3.0 million in 2020), mainly due to the collaboration with AstraZeneca which generated €9.9 million in revenues in 2021 (€2.9 million in 2020). This increase is related to the first license option exercised by AstraZeneca in 2021 for €7.1 million, for an oncolytic virus developed by Transgene.
Research tax credit amounted to €7.0 million in 2021 (€6.3 million in 2020).

– Net operating expenses of €40.9 million in 2021, compared to €33.9 million in 2020.
R&D expenses were €32.9 million in 2021 (€27.3 million in 2020). This increase is mainly due to the acceleration of clinical trials in 2021 and the start of a new process development project.
General and administrative expenses amounted to €7.4 million in 2021 (€6.5 million in 2020).

– Financial income of €4.0 million in 2021, compared to €6.8 million in 2020.
The partial sale of the Tasly BioPharmaceuticals shares in September 2021 generated a net gain on asset disposal of €1.3 million. Transgene’s remaining shareholding was revaluated and resulted in financial income of €2.4 million in 2021. This figure corresponds to the difference between the last market price compared with last year.

– Net loss of €19.5 million in 2021, compared to a net loss of €17.2 million in 2020.

– Net cash burn of €10.0 million in 2021 (excluding capital increase), compared to €17.0 million in 2020.

– Cash available at year-end 2021: €49.6 million, compared to €26.3 million at the end of 2020, following the completion of a €34.1 million private placement in June 2021. In addition, Transgene still holds Tasly BioPharmaceuticals shares valued at €18.9 million at the end of December 2021.

– Transgene has a financial visibility until the end of 2023.

The financial statements for 2021 as well as management’s discussion and analysis are attached to this press release (Appendices A and B).

The Board of Directors of Transgene met on March 16, 2022, under the chairmanship of Hedi Ben Brahim and closed the 2021 financial statements. Audit procedures have been performed by the statutory auditors and the delivery of the auditors’ report is ongoing.

The Company’s universal registration document, which includes the annual financial report, will be available early April 2022 on Transgene’s website, www.transgene.fr.

On March 16, 2022 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of investigational cancer immunotherapy PV-10 (rose bengal sodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) was presented at the annual conference of the European Neuroendocrine Tumor Society (ENETS), held from March 10-11, 2022 in a hybrid setting in Barcelona, Spain and online (Press release, Provectus Biopharmaceuticals, MAR 16, 2022, View Source [SID1234610179]).

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The oral presentation was made by the principal investigator of the clinical trial’s single center at The Queen Elizabeth Hospital (TQEH) in Adelaide, Australia: Tim Price, MBBS, DHlthSc (Medicine), FRACP, Head of Clinical Oncology Research and Chair of the combined Hematology and Medical Oncology Unit at TQEH, and Clinical Professor in the Faculty of Medicine at the University of Adelaide.

Highlights from the 2022 ENETS Presentation:

Patient characteristics
N = 12 patients: 50% male; median age of 66 years (range 47-79)
Primary tumor sites: 7 small bowel (58%), 3 pancreas (25%), 1 caecal (8%), and 1 unknown (8%; likely pancreas)
NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
All patients were refractory to SSA (100%), and 11 received PRRT (92%) as part of their prior treatment
All patients had symptomatic, progressive disease
Baseline chromogranin A (CgA): median 1,585 µg/L (range 35-10,370)
PV-10 treatment
4 patients (33%) received more than 1 dose (range 2-4)
8 patients (67%) received 1 dose
Safety
All treatment-emergent adverse events (TEAEs) were Grade 1 or 2, primarily injection site pain (75%)
Single subjects experienced Grade 3 TEAEs of photosensitivity reaction or transaminases increased
Efficacy
Median progression-free survival (mPFS): 9.4 months (range 1.0-41.8)
Median overall survival (mOS): 22.5 months (range 5.5-42.3); 4 patients alive
Subgroup analysis of primary NET histology, pancreas vs intestine: mPFS 2.7 months vs 19.7 months; mOS 11.8 months vs 25.5 months
Quality of life (QOL)
Stable or improved health status and symptoms after 3 months in most patients
A recording of Dr. Price’s presentation and a copy of his slides are available on Provectus’ website at View Source

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, said, "Study data continue to show encouraging local and systemic disease control, as well as symptom control, in a heavily pre-treated population and to support a role for monotherapy PV-10 as a treatment for neuroendocrine cancer patients who fail standard therapy."

Mr. Rodrigues added, "PV-10-led combination therapies for neuroendocrine cancer patients may represent opportunities to improve quality of life and clinical outcomes. Front-line approaches may include combining liver-directed PV-10 therapy with systemically-delivered immune checkpoint inhibitors to enhance PV-10’s immune mechanisms, or using PV-10 to enhance the activity of cytotoxic treatments such as peptide receptor radionuclide therapy."

About PV-10

Intralesional (IL) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days. This PV-10-induced functional T cell response may be enhanced and boosted in combination with immune checkpoint blockade (CB). In CB-refractory disease, PV-10 may restore disease-specific T cell function. IL PV-10 has been administered to over 450 patients with melanoma and cancers of the liver in both monotherapy and combination therapy settings. IL PV-10 is administered under visual, tactile, or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to visceral hepatic tumors.

Systemic administration of PV-10 is undergoing preclinical study as prophylactic and therapeutic treatments for high-risk and refractory adult solid tumor cancers, and as a therapeutic treatment for relapsed and refractory blood cancers.

On March 16, 2022 PharmaCyte Biotech, Inc. (NASDAQ: PMCB), a biotechnology company focused on developing cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported the financial and operational results for its third quarter ended January 31, 2022, and provided an overview of recent operational highlights (PharmaCyte’s Fiscal Year begins May 1 and ends April 30) (Press release, PharmaCyte Biotech, MAR 16, 2022, View Source [SID1234610178]).

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Cash Position: PharmaCyte had approximately $87 million in cash on hand as of January 31, 2022.

Recent Q3 Highlights—Corporate:

PharmaCyte established FDIC insured accounts of approximately $50.3 million.
Recent Highlights—Pipeline Products:

In November 2021, PharmaCyte announced that the empty capsule material that makes up its CypCaps pancreatic cancer product does not cause skin irritation.
In November 2021, PharmaCyte launched its malignant ascites program with the commencement of a pivotal study to determine if its treatment for locally advanced, inoperable pancreatic cancer (LAPC)—Cell-in-a-Box (CypCaps) combined with the cancer killing prodrug ifosfamide—can also delay the production and accumulation of malignant ascites.
In December 2021, the Company successfully completed the Cytochrome P450 site of integration DNA sequencing assay and announced the results of an additional, more detailed, analysis of the integration site of the cytochrome P450 2B1 gene from the augmented HEK293 cell clone that PharmaCyte uses in its CypCaps product.
In December 2021, PharmaCyte successfully completed the 36-month time point in its ongoing Master Cell Bank stability study.
In January 2022, PharmaCyte announced that the empty capsule material that makes up PharmaCyte’s CypCaps pancreatic cancer product candidate is not toxic for the encapsulated cells inside the CypCaps.
In February 2022, PharmaCyte provided a comprehensive update of the status of its Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA). Among other things, PharmaCyte reported on: (i) the ongoing stability studies of its clinical trial product CypCaps; (ii) the additional studies it has commenced in response to the FDA’s requests related to the clinical hold; (iii) the exact sequence of the Cytochrome P450 2B1 gene in its clinical trial product; (iv) the biocompatibility studies it has completed and that are underway; (v) micro-compression and swelling assays being conducted on its clinical trial product; (vi) break force and glide testing on its clinical trial product; (vii) studies to show that its clinical trial product is not adversely affected by the catheters interventional radiologists use to deliver the CypCaps to a patient; and (vii) tests to show that its clinical trial product is not affected by the contrast medium used by interventional radiologists to help guide the implantation of the CypCaps into a patient.
Recent Highlights—Financial:

As of January 31, 2022, PharmaCyte’s cash balance and total assets were approximately $87 million.

On January 31, 2022, PharmaCyte’s total stockholder equity was approximately $91 million.

PharmaCyte’s "Other Expenses" decreased by approximately $45,000 and $68,000 for the three and nine months ended January 31, 2022.

Operating expenses increased for the three months ended January 31, 2022, by approximately $99,000 and $297,000 for the nine months ended January 31, 2022, as compared to the prior fiscal year, due to costs associated with: (i) research and development (R&D); (ii) an uplist to Nasdaq Capital Markets; (iii) the closing of two public offerings for approximately $90 million; and (iv) and conducting studies related to lifting the FDA’s clinical hold on PharmaCyte’s proposed treatment for LAPC.

PharmaCyte’s R&D expenses increased from the start of its fiscal year to about $526,000 to date. The two capital raises PharmaCyte conducted in August 2021 allowed for these necessary expenses to be possible.

To learn more about PharmaCyte’s pancreatic cancer treatment and how it works inside the body to treat locally advanced, inoperable pancreatic cancer, we encourage you to watch the company’s documentary video complete with medical animations at: View Source

On March 16, 2022 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported financial results for the fourth quarter and full year 2021 and provided an update on recent corporate activities (Press release, Sunesis, MAR 16, 2022, View Source [SID1234610176]).

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"In 2021, we achieved key corporate and clinical milestones that we believe positioned us for an exciting year ahead," said Ivor Royston, M.D., President and Chief Executive Officer of Viracta. "We entered the public market while simultaneously completing a successful equity financing, and initiated two clinical studies of our all-oral combination therapy, Nana-val. These included our pivotal NAVAL-1 trial in EBV-positive relapsed/refractory lymphoma and our Phase 1b/2 trial in advanced EBV-positive solid tumors. In addition, we ended the year by presenting final data from Nana-val’s Phase 1b/2 EBV-positive lymphoma trial in an oral presentation at ASH (Free ASH Whitepaper) 2021, which showed complete responses in a heavily pre-treated patient population in need of a new therapeutic option."

Dr. Royston continued, "In the year ahead, we anticipate several important advancements and milestones in our clinical programs, including meaningful progress in NAVAL-1, and a preliminary data readout from our ongoing Phase 1b/2 trial in solid tumors. Should we see early efficacy signals for Nana-val in solid tumors, as we did in the Phase 1b/2 EBV-positive lymphoma trial, it could serve as initial support for our pursuit of a tissue agnostic approach to EBV-associated malignancies and expand our addressable patient population. With a cash runway into mid-2024, we are well capitalized to execute on these milestones and our broader corporate strategy."

Fourth Quarter 2021 and Recent Highlights
Clinical

Presented final results from the Phase 1b/2 trial of Nana-val (nanatinostat and valganciclovir) in relapsed/refractory (R/R) EBV+ lymphoma, in an oral presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Data featured in the presentation were from 55 patients with a median of two prior therapies. 75% (41/55) of patients were refractory to their last therapy, and 96% (53/55) had exhausted all standard therapies (per Investigator).
Efficacy data in evaluable patient (n=43):

Across all lymphoma subtypes: overall response rate (ORR) = 40% (17/43); complete response (CR) = 19% (8/43)
T/NK- non-Hodgkin lymphoma: ORR = 60% (9/15); CR = 27% (4/15)
Extranodal NK/T-Cell Lymphoma (ENKTL): ORR = 63% (5/8); CR = 13% (1/8)
Peripheral T-cell lymphoma (PTCL)/ Angioimmunoblastic T-cell lymphoma (AITL): ORR = 67% (4/6); CR = 50% (3/6)
Diffuse large B cell lymphoma (DLBCL): ORR = 67% (4/6); CR = 33% (2/6); Both DLBCL complete responses were in patients refractory to first line R-CHOP
Immunodeficiency-associated lymphoproliferative disorders (IA-LPD): ORR = 50% (3/6); CR = 33% (2/6)
Median duration of response was 10.4 months
Nana-val was generally well tolerated with reversible low-grade toxicities. The most commonly reported treatment emergent adverse events were reversible cytopenias, low grade creatinine elevations, and gastrointestinal symptoms.

Continued enrollment into, and global expansion of, pivotal NAVAL-1 trial of Nana-val for the treatment of R/R EBV+ lymphoma. NAVAL-1 employs a Simon two-stage design where patients are initially enrolled into six cohorts based on lymphoma subtype in Stage 1. If a pre-specified activity threshold is reached, additional patients will be enrolled in Stage 2. Lymphoma subtypes demonstrating promising activity in Stage 2 may be further expanded. If successful, the Company believes NAVAL-1 could potentially support multiple new drug application (NDA) filings across various EBV+ lymphoma subtypes. The Company anticipates providing an update on the initial cohort(s) that expand into Stage 2 in the second half of 2022.
Dosed first patient in the Phase 1b/2 trial of Nana-val for the treatment of EBV+ recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) and other EBV+ solid tumors. The Phase 1b dose escalation portion of the study will evaluate safety and determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with EBV+ R/M NPC. In Phase 2, up to 60 patients with EBV+ R/M NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to evaluate safety and preliminary efficacy. Additionally, patients with other EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort. Viracta anticipates reporting preliminary Phase 1b safety and efficacy data from the trial in the second half of 2022.
Received orphan drug designation (ODD) from U.S. Food and Drug Administration (FDA) for Nana-val for the treatment of EBV+ Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS). This represents the first ODD for EBV+ DLBCL, NOS granted by the FDA, and the fourth ODD granted for Nana-val overall. The FDA previously granted ODD to Nana-val for the treatment of T-cell lymphoma, post-transplant lymphoproliferative disorder and plasmablastic lymphoma.
Preclinical

Presented preclinical data on vecabrutinib, a reversible inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK), at the 2021 ASH (Free ASH Whitepaper) Annual Meeting. Two presentations were featured, oral and poster, with data that demonstrate the capacity of vecabrutinib to modulate immune responses. Data featured in the oral presentation showed vecabrutinib enhancing the efficacy of chimeric antigen receptor (CAR) T-cells in a murine mantle cell lymphoma model. Vecabrutinib also inhibited secretion of pro-inflammatory cytokines known to cause toxicities associated with CAR T-cell therapy, an observation that was consistent with data from a prior Phase 1 clinical trial evaluating vecabrutinib as a treatment for patients with B-cell malignancies. Data featured in the poster presentation show vecabrutinib significantly reducing signs of sclerodermatous chronic graft versus host disease (cGVHD), including skin irritation, redness, alopecia, and diarrhea, via modulation of pathogenetic B- and T-cell subsets in a murine disease model.
Corporate

Announced addition to the Nasdaq Biotechnology Index (NBI). The NBI is designed to track the performance of a set of securities listed on The Nasdaq Stock Market (Nasdaq) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The NBI is re-ranked each year and is calculated under a modified capitalization-weighted methodology. Additionally, the NBI forms the basis for a number of Exchange Traded Funds (ETFs).
Secured expanded $50 million credit facility from Silicon Valley Bank (SVB) and Oxford Finance. The credit facility replaces Viracta’s prior $15 million loan and security agreement with SVB and provides the Company with the option to obtain additional non-dilutive funding at a single-digit cost of capital. Through this expanded credit facility, the Company’s existing $5.0 million debt balance was refinanced. The remaining $45.0 million is available to the Company, which is under no obligation to draw funds in the future.
Anticipated 2022 Milestones
Provide preliminary Phase 1b safety and efficacy data from the Phase 1b/2 trial in advanced EBV+ solid tumors: 2H 2022
Update on NAVAL-1 cohort(s) progressing from Stage 1 to Stage 2: 2H 2022
Fourth Quarter and Full Year 2021 Financial Results
Cash Position – Cash and cash equivalents totaled approximately $103.6 million as of December 31, 2021, which Viracta expects will be sufficient to fund its operations into mid-2024, excluding any additional borrowings under the $50.0 million credit facility.
Research and development expenses – Research and development expenses were approximately $7.3 million and $3.6 million for the fourth quarters ended 2021 and 2020, respectively. Research and development expenses were approximately $23.9 million and $13.5 million for years ended December 31, 2021, and December 31, 2020, respectively. The increase in research and development expenses was primarily due to increases in costs incurred to support the initiation of the NAVAL-1 and solid tumor trials as well as an increase in headcount and non-cash share-based compensation.
Purchased and acquired in-process research and development – Purchased and acquired in-process research and development expenses were $88.5 million for the year ended December 31, 2021. The expenses were related to the $4.0 million payment associated with the termination of the collaboration and license agreement with Shenzhen Salubris Pharmaceutical Co. Ltd. and non-cash and non-recurring costs of $84.5 million related to the write-off of in-process research and development acquired in the merger with Sunesis Pharmaceuticals.
General and administrative expenses – General and administrative expenses were approximately $4.0 million and $2.6 million for the fourth quarters ended 2021 and 2020, respectively. General and administrative expenses were approximately $15.4 million and $5.3 million for the years ended December 31, 2021, and December 31, 2020, respectively. The increase was largely due to significant and non-recurring costs associated with the merger, in addition to incremental costs associated with being a publicly traded company, including legal fees, audit fees, consulting expenses, filing fees and increased directors’ and officers’ insurance costs, in addition to an increase in non-cash share-based compensation.
Gain on Royalty Purchase Agreement – Gain on Royalty Purchase Agreement the year ended December 31, 2021, was associated with upfront proceeds of $13.5 million received in connection with the multi-license milestone and royalty monetization transaction with XOMA Corporation in March 2021.
Adjusted loss from operations – Adjusted loss from operations for the year ended December 31, 2021, excluding the non-recurring operating expenses associated with the write-off of in-process research and development acquired in the merger and the termination agreement with Salubris Pharmaceutical Co. Ltd. (a non-GAAP measure) was $25.8 million, compared to a loss from operations of $114.3 million. There is not a comparative adjustment to loss from operations for the same period in 2020.
Net loss – Net loss was approximately $11.4 million, or $0.31 per share (basic and diluted), and approximately $6.3 million, or $13.31 per share (basic and diluted), for the fourth quarters ended 2021 and 2020, respectively. Net loss was approximately $114.8 million, or $3.60 per share (basic and diluted) for the year ended December 31, 2021, compared to a net loss of approximately $19.0 million, or $58.56 per share (basic and diluted) for the year ended December 31, 2020.
About Nana-Val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which is key to inducing viral genes that are epigenetically silenced in EBV-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-Val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed/refractory EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 trial in patients with EBV+ recurrent or metastatic nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden and is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

About Vecabrutinib
Vecabrutinib is a well-tolerated, selective, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Vecabrutinib is being studied as a potential enhancer of efficacy and safety of CAR T-cell therapy.

On March 16, 2022 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for SON-1010, a proprietary version of Interleukin 12 (IL-12) configured using Sonnet’s Fully Human Albumin Binding (FHAB) technology (Press release, Sonnet BioTherapeutics, MAR 16, 2022, View Source [SID1234610175]). This will allow Sonnet to initiate its First-in-Human Phase 1 trial in adult oncology patients in the second quarter of 2022.

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"The FDA’s acceptance of the IND for SON-1010 is an important milestone in the development of our lead FHAB asset, signifying the evolution of Sonnet into a clinical biopharmaceutical company," said Pankaj Mohan, Ph.D., Founder and Chief Executive Officer. "We are excited about the progress we have made with our FHAB platform, which we believe will set the stage for improved efficacy of monospecific and bispecific cytokines, each differentiated by tumor targeting and retention in the tumor microenvironment."

The planned Phase 1 trial will be a multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SON-1010 in adult patients with advanced solid tumors. "We have worked hard to establish a dose range for this extended PK form of IL-12 that can be tested safely and may provide an enhanced therapeutic index," said Richard Kenney, M.D., Sonnet’s Chief Medical Officer. "The goal of this strategy is to carefully adjust the body’s cells and cytokines to enhance the innate immune response to tumors." The study, utilizing a standard 3+3 oncology design in at least 5 cohorts, will establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) using monthly subcutaneous injections of SON-1010. The primary endpoint will assess the safety and tolerability of SON-1010, with key secondary endpoints planned to measure PK, PD, immunogenicity, and anti-tumor activity.