On August 18, 2020 Avacta Group plc (AIM: AVCT), the developer of Affimer biotherapeutics and reagents, reported the expansion of its existing multi-target collaboration and development agreement with LG Chem Life Sciences (LG Chem), the life sciences division of the South Korean LG Group, to include new programmes incorporating Avacta’s Affimer XT serum half-life extension system (Press release, Avacta, AUG 18, 2020, View Source [SID1234563784]).

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In December 2018, Avacta and LG Chem entered into a multi-target therapeutics development agreement to develop Affimer therapeutics in several disease areas potentially worth over $300m to Avacta. The companies have today agreed to expand this drug development partnership to include Avacta’s Affimer XT technology, which can be used to control the time a drug spends in the circulation.

The expansion of the partnership includes an undisclosed additional upfront payment, plus near-term pre-clinical milestones and longer-term clinical development milestones totaling $98.5m for two therapeutics to be developed using the Affimer XT technology. Under the terms of the extended agreement, LG Chem has the exclusive rights to develop and commercialise, on a world-wide basis, Avacta’s Affimer PD-L1 inhibitor with Affimer XT serum half-life extension.

The expanded partnership also provides LG Chem with rights to develop and commercialise other Affimer and non-Affimer biotherapeutics combined with Affimer XT half-life extension for a range of indications and Avacta could earn up to $55m in milestone payments for each of these new products. In addition, under the agreement Avacta will earn royalties on all future Affimer XT product sales by LG Chem.

Dr. Alastair Smith, Chief Executive of Avacta Group commented: "I am delighted with this expansion to the agreement with LG Chem, with whom we have developed a strong collaborative partnership. LG Chem is a world-class drug development partner with excellent biologics manufacturing and clinical development capabilities and a pioneering vision to develop innovative therapies.

The expansion of our collaboration to develop new therapies for patients with cancer and other diseases is another strong validation of the Affimer technology and its potential as a therapeutic platform to deliver a pipeline of new drugs.

We look forward to developing these new therapies with our partners, LG Chem, and I look forward to updating the market on this and our other drug development and diagnostics progammes in due course."

This announcement contains information which, prior to its disclosure, was considered inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (MAR).

On August 18, 2020 Ultimovacs ASA ("Ultimovacs", ticker ULTIMO), a pharmaceutical company developing novel immunotherapies against cancer, reported that patient enrollment has been completed in the ongoing US-based Phase I clinical trial testing Ultimovacs’ lead candidate, UV1, in combination with pembrolizumab as first line treatment in patients with metastatic malignant melanoma (Press release, Ultimovacs, AUG 18, 2020, View Source [SID1234563783]). The study was designed to assess the safety and tolerability of UV1 combined with checkpoint inhibitor pembrolizumab and to explore initial signs of clinical response.

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The Phase I trial investigates Ultimovacs’ cancer vaccine, UV1, in combination with PD-1 checkpoint inhibitor, pembrolizumab. Pembrolizumab is standard-of-care therapy for malignant melanoma, improving the ability of immune cells to kill tumor cells. The preliminary safety information obtained from the first 20 patients in the Phase I trial allowed for the exploration of a higher dose of the adjuvant GM-CSF in 10 additional patients. The first 20 patients received 37.5 μg GM-CSF per UV1 vaccination versus 75 μg GM-CSF per UV1 vaccination in the second cohort of 10 patients. GM-CSF is used as an adjuvant together with UV1 to strengthen the ability of UV1 to stimulate the immune system. With 30 patients enrolled and treated as of today, the trial reached its targeted enrollment criteria. No unexpected safety issues related to UV1 have been observed to date and UV1 has generally been well tolerated by the patients.

Carlos de Sousa, Chief Executive Officer at Ultimovacs, commented:
"Early data on the patients enrolled in the Phase I trial of UV1 in combination with pembrolizumab demonstrate a strong safety profile to date and provide further support for Ultimovacs’ approach of combining UV1 treatment with checkpoint inhibitors. The preliminary safety data builds further on a previous Phase I trial in malignant melanoma, where UV1 was combined with the CTLA-4 checkpoint inhibitor ipilimumab. In both combination trials, treatment with UV1 has been well tolerated by patients, providing a solid basis for the triple combination of UV1 with CTLA-4 and PD-1, which is currently investigated in the Company’s Phase II trials INITIUM and NIPU. We are proud of the Company’s progress and would like to thank the patients, their families and healthcare providers for their participation, particularly in the current challenging environment. "

Jens Bjørheim, Chief Medical Officer of Ultimovacs, added:
"We are pleased that we have completed the enrollment of the second cohort in this Phase I trial despite challenging times related to the ongoing pandemic. In September of this year, all patients in the first cohort will have reached their 1-year follow-up period and we look forward to announcing top-line safety and preliminary efficacy data from patients in the first cohort in the fourth quarter of this year, followed by more detailed results at an international medical conference early next year."

About UV1 and the UV1 Phase II Clinical Trials
UV1 is a peptide-based vaccine inducing a specific T cell response against the universal cancer antigen, telomerase. UV1 is being developed as a therapeutic cancer vaccine which may serve as a platform for use in combination with other immuno-oncology drugs which require an ongoing T cell response for their mode of action. To date, UV1 has been tested in four Phase I clinical trials in a total of 82 patients and maintained a positive safety and tolerability profile as well as encouraging signals of efficacy.

UV1 will be tested in three different randomized Phase II trials:

The INITIUM trial is an Ultimovacs-sponsored, global, randomized Phase II trial for patients with metastatic malignant melanoma. Patients will be treated with UV1 in combination with ipilimumab (CTLA-4 checkpoint inhibitor) and nivolumab (PD-1 checkpoint inhibitor). The trial will be conducted in the U.S. and Europe, including Norway. The first patient was dosed on 15 June 2020. A total of 154 patients will be enrolled in the study, 77 patients will receive nivolumab and ipilimumab and the second half of the patients will receive nivolumab, ipilimumab and UV1. The primary endpoint for the study is progression-free survival and the planned readout of the primary endpoint is in the second half of 2022.
The NIPU trial is a randomized, multi-center Phase II trial in which the universal cancer vaccine, UV1, is investigated in combination with the checkpoint inhibitors, ipilimumab and nivolumab, as second-line treatment in mesothelioma. Oslo University Hospital is the sponsor of the NIPU study. Bristol-Myers Squibb and Ultimovacs have entered into agreements with OUS to support the preparations and execution of the trial. The first patient was dosed on 15 June 2020. A total of 118 patients will be included in the NIPU study. Half of the patients will be treated with the combination of UV1, ipilimumab (CTLA-4 checkpoint inhibitor) and nivolumab (PD-1 checkpoint inhibitor), whereas the other half will receive nivolumab and ipilimumab only. The study is planned to be conducted at six national hospital centers specialized in treating mesothelioma in four countries (Norway, Sweden, Denmark and Australia). Planned readout of the primary endpoint progression-free survival is the second half of 2022.
A third Phase II clinical trial will evaluate UV1 in a new cancer indication in combination with indication-specific standard of care cancer therapies different from those to be tested in INITIUM (malignant melanoma, 154 patients) and NIPU (mesothelioma, 118 patients). In the collaboration, Ultimovacs will supply UV1 and a big pharma company will supply its proprietary cancer treatment to the clinical trial group which will sponsor the trial.
The Phase II clinical program builds on three completed Phase I trials and one ongoing Phase I trial. The Phase II trials will evaluate UV1 in three different indications in more than 400 patients and in collaboration with two big pharma companies. The ongoing and planned clinical trials represent a strong platform for Ultimovacs to advance towards a potential registration of the universal cancer vaccine, UV1.

On August 18, 2020 EDAP TMS SA (Nasdaq: EDAP) ("the Company"), the global leader in robotic energy-based therapies, reported that two papers highlighting successful studies of the Company’s high intensity focused ultrasound (HIFU) technology for the effective ablation of prostate cancer tissue have been accepted for publication in the prestigious peer-reviewed Journal of Urology, the official journal of the American Urology Association (AUA) (Press release, EDAP TMS, AUG 18, 2020, View Source [SID1234563782]). The two studies, scheduled for publication in the September and October paper editions of the journal, detail clinical outcomes from HIFU procedures conducted at the first two hospitals to purchase the Ablatherm device in the US shortly after the FDA clearance at the end of 2015.

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Details of the publications are as follows:

High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer: Initial Outcomes of a United States Series. Andre Abreu et al., USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California.

This study describes a study of 100 men with a confirmed diagnosis of prostate cancer, 72% of whom were diagnosed with intermediate or high-risk disease. All study subjects underwent hemi-gland ablation with HIFU as primary treatment for prostate cancer between December 2015 and December 2019. Radical treatment was avoided in 91% of men at two years. There were no major complications, and no rectal fistulas occurred. The study found that urinary symptoms returned to near baseline questionnaire scores within 3-6 months and sexual function returned to baseline by 12 months.

"We are pleased to present this first and largest US study on focal therapy with HIFU as primary treatment for prostate cancer," said Andre Abreu, MD, Assistant Professor of Clinical Urology and Radiology, USC Institute of Urology, and first author of the publication. The results observed from these first 100 prostate cancer patients treated with HIFU partial gland ablation in the US are consistent with the very encouraging results from studies conducted in Europe, both in terms of disease control and genitourinary function preservation. After two years of follow-up, 91% of patients avoided radical treatment and its inherently debilitating side effects. Additionally, all patients maintained full continence and there was no significant decline of erectile function and no major adverse events occurred. This reaffirms our commitment to bringing personalized prostate cancer management, incorporating patients’ preference and implementing a risk-adaptive approach, with adequate cancer control and without compromising patients’ quality of life."

Prospective Evaluation of Focal High Intensity Focused Ultrasound for Localized Prostate Cancer. B. Nahar et al., Department of Urology, University of Miami Miller School of Medicine, Miami, Florida, Sylvester Comprehensive Cancer Center.

This paper describes a single-center prospective study of 52 prostate cancer patients who underwent HIFU treatment between January 2016 and July 2018. Sixty seven percent of study subjects were diagnosed with intermediate or high-risk disease (Grade Group 2 or greater). All patients were treated with EDAP’s Ablatherm HIFU device and were followed for a minimum of 12 months post-procedure. Biopsies were performed at 6 or 12 months for high or low/intermediate risk cancers, respectively. Two years post procedure, only one patient (2%) had to undergo radical prostatectomy surgery. No change in continence was observed and sexual function returned to baseline at 12 months.

The full abstract is available online at: View Source

Marc Oczachowski, Chairman and Chief Executive Officer of EDAP, commented: "The very positive results of these two studies – the first published in the United States – add to the significant amount of data demonstrating that our HIFU technology, now led by our latest generation Focal One device, provides unmatched potency and accuracy, thereby eliminating the two most devastating side effects of radical surgery – incontinence and impotence. Importantly, these results are consistent with previously completed European studies that included larger patient cohorts and longer follow-up periods. The fact that these two prestigious academic institutions, based on these early positive clinical results, have both decided to invest in Focal One is a clear sign of the potential of EDAP’s HIFU technology."

"We are encouraged to see the continuous adoption and use of our US installed base of HIFU machines. Seeing some of our prominent reference centers already publishing in top-ranked Journals their results with our HIFU technology is clearly another milestone in our US market penetration strategy," Mr. Oczachowski concluded.

On August 18, 2020 Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) reported that it has dosed the first patient in AROHIF21001, a Phase 1b dose-finding clinical study of ARO-HIF2, the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with clear cell renal cell carcinoma (ccRCC) (Press release, Arrowhead Pharmaceuticals, AUG 18, 2020, View Source [SID1234563781]).

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Javier San Martin, M.D., chief medical officer at Arrowhead, said: "This Phase 1b study is designed to provide us with a robust readout on safety and dose response of ARO-HIF2, and may also deliver signals on preliminary efficacy in an advanced ccRCC patient population. Most patients with ccRCC, one of the most common forms of kidney cancer, have an inactivated mutation in the Von Hippel-Lindau gene rendering them unable to degrade HIF-2α, which leads to an increase in activity during tumor hypoxia and promotes tumor growth. We believe that HIF-2α is an attractive target for RNAi-based gene silencing and, more broadly, we are eager to achieve clinical validation for our tumor targeted TRiM-enabled RNAi therapeutics so we can address additional unmet needs in oncology. We also recently announced that ARO-ENaC, our investigational RNAi therapeutic targeting cystic fibrosis, started dosing in a Phase 1/2 study. This means that our TRiM platform is now being studied in three different tissue types in human clinical trials. This is very exciting for us at Arrowhead and, we think, represents a significant step towards reaching the full therapeutic potential of RNA interference."

AROHIF21001 (NCT04169711) is a Phase 1b dose-finding clinical study in up to 18 patients with advanced ccRCC to evaluate the safety of ARO-HIF2 and to determine the recommended Phase 2 dose. Secondary objectives include the assessment of pharmacokinetics and preliminary efficacy, based on Response Evaluation Criteria in Solid Tumors (RECIST). Exploratory objectives for AROHIF21001 are post-dose tumoral expression of HIF genes in response to treatment with ARO-HIF2, change in Karnofsky Performance Status (KPS), correlation of tumor response based on RECIST with tumor HIF2α gene expression and tumor integrin expression, correlation of integrin expression with changes in HIF gene expression, evaluation of serum biomarkers of ARO-HIF2 activity, correlation of RCC-related gene expression to ARO-HIF2 activity, and evaluation of plasma and urine metabolites.

On August 18, 2020 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a pharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the second quarter of 2020 and associated Company developments (Press release, Supernus, AUG 18, 2020, View Source [SID1234563779]).

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Commercial Update

Second quarter 2020 net product sales of $124.0 million, 21% higher than the same period in 2019, driven by higher net product sales of Trokendi XR and Oxtellar XR and the addition of $10.6 million of net product sales from the acquired PD products. Net product sales of Trokendi XR and Oxtellar XR increased 11% compared to the same period in 2019 due to the beneficial impact of lower gross-to-net sales deductions in the second quarter of 2020, coupled with the price increase taken in January 2020. The year over year impact of volume, on an extended units basis (i.e., number of capsules/tablets), was neutral.

Corporate and Product Pipeline Update

SPN-812 – Novel non-stimulant for the treatment of ADHD in children and adults

The Company continues to prepare for the commercial launch of SPN-812, with shipments to the trade in December 2020. The Company remains engaged with the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for the treatment of ADHD. The NDA Prescription Drug User Fee Act (PDUFA) target action date is November 8, 2020.
Recruitment has resumed in the Phase III program in adult patients, after being put on hold in March 2020 due to the impact of the COVID-19 pandemic. The trial is expected to complete enrollment this year, with topline data expected in the first quarter of 2021.
SPN-830 (Apomorphine infusion pump) – continuous treatment of motor fluctuations ("on-off" episodes) in PD

NDA submission is expected in the fourth quarter of 2020, with launch, if approved by the FDA, in the second half of 2021.
SPN-820 – novel first-in-class activator of mTORC1

Preclinical and development activities are ongoing, with the initiation of the Phase II clinical program in patients with treatment-resistant depression targeted for the second half of 2021.
Operating Expenses

Second Quarter

Research and development (R&D) expenses in the second quarter of 2020 were $22.2 million, compared to $17.0 million in the same quarter last year. This increase was primarily due to the $10.0 million option fee paid to Navitor as part of the collaboration agreement for SPN-820, coupled with expenses incurred in the SPN-812 Phase III program for adults. Increased expenses were partially offset by reduced spending for the SPN-810 Phase III trials.

Selling, general and administrative (SG&A) expenses in the second quarter of 2020 were $48.1 million, compared to $39.8 million in the same quarter last year. This increase is primarily due to $7.4 million of expense associated with the transaction to acquire the CNS portfolio of US WorldMeds in the second quarter of 2020, partially offset by $3.1 million in PDUFA fee refund from the FDA.

Operating Earnings and Earnings Per Share

Operating earnings (GAAP) in the second quarter of 2020 were $45.5 million, compared to $42.6 million in the second quarter of 2019. The increase was primarily due to increased net product sales, partially offset by the aforementioned option fee paid to Navitor and acquisition-related expenses associated with the acquired PD products.

Net earnings (GAAP) in the second quarter of 2020 were $34.7 million, or $0.65 per diluted share, as compared to $32.7 million, or $0.61 per diluted share, in the same period last year. Net earnings (GAAP) were subject to a higher effective tax rate of 27% in the second quarter of 2020 relative to the second quarter of 2019, due to the aforementioned transaction-related expenses associated with the acquired PD products, which are partially tax deductible, and an increase in the number of states in which the Company pays income tax.

Weighted-average diluted common shares outstanding were approximately 53.6 million for the second quarter of 2020, as compared to approximately 53.9 million for the prior year period.

Balance Sheet Highlights

As of June 30, 2020, the Company had $733.5 million in cash, cash equivalents, marketable securities and long term marketable securities, compared to $938.8 million at December 31, 2019. During the first six months of 2020, inclusive of net changes in working capital, the Company generated $100.9 million of cash from operations. During the second quarter, the Company made cash payments of approximately $300 million for the acquired PD products, as well as the aforementioned $10.0 million fee paid to Navitor as part of the development and option agreement for SPN-820.

Financial Guidance

Guidance was suspended in May 2020 due to several factors: the uncertainty caused by the COVID-19 pandemic; the second quarter 2020 acquisition of the PD products; and the impact of the partnership with Navitor. The Company is now reinstating and updating full year 2020 financial guidance, which consists of the following components, inclusive of the impact of acquiring the PD products as of June 9, 2020:

Net product sales to range from $460 million to $500 million, including approximately $80 million from the PD products.
Gross margins of approximately 90%.
R&D expenses of approximately $85 million.
Selling, general and administrative expenses to range from $240 million to $250 million.
Operating earnings (GAAP) to range from $90 million to $110 million, which includes amortization of intangible assets of approximately $15 million.
Conference Call Details

The Company will hold a conference call hosted by Jack Khattar, President and Chief Executive Officer, and Greg Patrick, Senior Vice President and Chief Financial Officer, to discuss these results at 9:00 a.m. Eastern Time, on Wednesday, August 19, 2020.

Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.

Conference dial-in: (877) 288-1043
International dial-in: (970) 315-0267
Conference ID: 5175177
Conference Call Name: Supernus Pharmaceuticals Second Quarter 2020 Earnings Conference Call
Following the live call, a replay will be available on the Company’s website, www.supernus.com, under "Investor Relations".