On February 13, 2020 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, oncology therapeutics company developing onvansertib for the treatment of various cancers including prostate, colorectal, and leukemia, reported positive data from its ongoing Phase 2 trial of onvansertib in combination with Zytiga (abiraterone – Johnson & Johnson)/prednisone, all administered orally, for the treatment of patients with Zytiga-resistant metastatic castration-resistant prostate cancer (mCRPC) (Press release, Trovagene, FEB 13, 2020, View Source [SID1234554296]).

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The clinical data, featured in a poster presentation today at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Genitourinary Cancers Symposium in San Francisco, further demonstrates the efficacy of onvansertib in patients who develop resistance to first-line treatment with Zytiga. Onvansertib addresses Zytiga resistance across known androgen receptor (AR) resistance mechanisms. In patients with AR alterations, 86% had decreases in PSA levels with the addition of onvansertib to daily Zytiga.

"Metastatic castration-resistant prostate cancer is the second leading cause of cancer-related death among men in the United States, and unfortunately many patients are in desperate need of new treatment options," said study principal investigator Dr. David Einstein, Genitourinary Oncology Program, Beth Israel Deaconess Medical Center. "These data show that adding onvansertib to abiraterone in metastatic castration-resistant prostate cancer patients with an early resistance to abiraterone validates pre-clinical studies and shows potential as a new therapeutic option."
"We are very encouraged by the significant decreases in circulating tumor cells (CTCs) with the addition of onvansertib, given that these changes in CTCs are an accepted surrogate prognostic factor for efficacy and survival," said Dr. Mark Erlander, Chief Scientific Officer at Trovagene. "In addition, observing efficacy in patients that have tumors exhibiting known mechanisms of resistance to ARS inhibitor, Zytiga, suggests that onvansertib’s activity could extend to overcoming resistance to other ARS inhibitors such as Xtandi and Erleada."
Key Presentation Highlights:
Efficacy

Overall, across both arms (A and B), a 63% (12 of 19) response (Stable Disease – SD and Partial Response – PR) was observed in patients evaluable for efficacy (completed 12 weeks of treatment with onvansertib + Zytiga (abiraterone)/prednisone); 6 patients have been on treatment for ≥7 months

Arm B (onvansertib dosed daily on days 1-5 in a 14-day cycle)

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80% (4 of 5) patients had SD at 12 weeks, with 3 patients achieving the efficacy endpoint (PSA stabilization) and 3 patients remain on treatment

60% (3 of 5) patients have or had progression-free survival of >7 months

Arm A (onvansertib dosed daily on days 1-5 in a 21-day cycle)

57% (8 of 14) patients had SD or PR at 12 weeks, with 5 patients achieving the efficacy endpoint (PSA stabilization) and 4 patients remain on treatment

21% (3 of 14) patients have or had progression-free survival; 2 patients remain on treatment for >1 year

Onvansertib-induced circulating tumor cell (CTC) decrease is associated with progression-free survival

CTC count, reported as favorable or unfavorable (<5 versus ≥5 CTC/7.5mL of blood, respectively) is a prognostic factor for survival in CRPC and the conversion from unfavorable to favorable is associated with improved survival
o
At baseline, 25 (78%) patients had unfavorable CTC count with median of 19 CTC/7.5mL

10 of the unfavorable patients were re-analyzed after 12 weeks of treatment

5 (50%) patients had a ≥80% CTC decrease, including 2 AR-V7+ patients

4 (40%) patients converted from unfavorable to favorable CTC level (<5 CTC/7.5mL)

3 (30%) patients had no detectable CTC

Median time on treatment for patients with decrease CTC (n=4) is 7 months to-date, with 4 patients remaining on treatment

Conversely, median time on treatment for patients with increase CTC (n=5) was 5 months, and none of these patients remain on treatment

Efficacy observed in patients with Zytiga-resistant androgen receptor (AR) alterations

AR mechanisms of resistance to abiraterone include the expression of the constitutively active AR splice variant AR-V7 and the AR gain-of function point mutation T878A

Among the 19 patients who completed the 12-week treatment (Arm A + B):

5 patients were AR-V7+ at baseline

2 patients had AR T878A mutations at baseline

Onvansertib showed efficacy in patients with AR alterations (N=7):

6 (86%) patients had a decrease in PSA levels with the addition of onvansertib

4 (57%) patients had SD or PR at 12 weeks with 3 (43%) patients achieving the primary efficacy endpoint

3 patients have or had progression-free survival of >7 months, 2 patients remain on treatment

Safety

Safety lead-in cohort was completed in Arm A at 24 mg/m2 and is ongoing in Arm B at 18 mg/m2

Most frequent G3/G4 AEs were expected, on-target, reversible hematological (anemia, neutropenia, thrombocytopenia and leukopenia), associated with the mechanism of action of onvansertib

Hematological AEs were reversible and effectively managed by dose delay, dose reduction and/or growth factor support

Grade 3 hypophosphatemia was reported in 3 patients, next cycle treatment was delayed for 2 patients to allow recover
Conclusions

Overall, across both arms (A and B), a 63% (12 of 19) response (SD + PR) was observed in patients evaluable for efficacy (completed 12 weeks of treatment); 6 patients have been on treatment for ≥7 months

Onvansertib induced profound CTC decreases in patients with unfavorable CTC count (>80% decrease in 5 of 10 patients tested); CTC decrease was associated with prolonged response to treatment and progression-free survival

6 of 7 patients with AR alterations (AR-V7+ or AR T878A) had an immediate decrease in PSA following onvansertib treatment; efficacy (SD+PR) was achieved in 57% (4 of 7) patients

In both arms (A and B) onvansertib in combination with abiraterone was safe and well-tolerated

A more continuous dosing schedule (Arm C – onvansertib 12 mg/m2 on days 1-14 of a 21-day cycle) is planned to evaluate safety and efficacy

Adding onvansertib to abiraterone in mCRPC patients resistant to abiraterone (rising PSA) validates pre-clinical studies and shows promise as a new therapeutic option
About the Phase 2 Trial of Onvansertib in Metastatic Castration-Resistant Prostate Cancer
The trial is a Phase 2 open-label study of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone, all administered orally, in patients with metastatic castration-resistant prostate cancer (mCRPC), showing signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on Zytiga (NCT03414034). The primary efficacy endpoint is the proportion of patients achieving disease control after 12 weeks of study treatment, as defined by lack of prostate specific antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving abiraterone acetate and prednisone. The trial is being conducted by Beth Israel Deaconess Medical Center (BIDMC), Dana-Farber Cancer Institute (Dana-Farber), and Massachusetts General Hospital Cancer Center (MGH). David Einstein, MD, Genitourinary Oncology Program at BIDMC, is the principal investigator for the trial.
About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.
Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410) and a Phase 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.
Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On February 13, 2020 Riptide Bioscience, Inc., reported the publication in Science Translational Medicine of a seminal article establishing a novel immune checkpoint, potentially useful in the treatment of both cancer and fibrosis (Press release, Riptide Bioscience, FEB 13, 2020, View Source [SID1234554312]).

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"We’re now engaging with larger pharmaceutical companies to move this important program into clinic. I see a real opportunity, similar in many ways to the discovery of the first checkpoint inhibitors, to make a major impact on clinical practice."

The article is entitled "Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and immune antitumor immune responses." (View Source). Riptide originated the development program and collaborated with Tuskegee University’s Cancer Research Center and the National Institutes of Health under separate research agreements. First author, Dr. Jesse Jaynes, Professor of Integrative Biosciences at Tuskegee, was joined by 42 co-authors from the National Cancer Institute, the National Center for Advancing Translational Sciences, and Tuskegee in this publication.

The article documents extensive research to evaluate the efficacy and confirm the mechanism of Riptide drug candidate RP-182. RP-182 is the first of several engineered peptides emerging from a years-long effort to enhance the activity of naturally occurring host defense peptides (HDPs) with immunomodulatory properties.

HDPs have the capacity to directly kill invasive microbes by forming pores in their membranes. However, certain HDPs also activate the immune system to fight the invaders – an activity which Riptide scientists discovered could be turned against "non-self" cancer cells.

Jaynes commented, "We did an extensive search for the cellular target of these peptides. Surprisingly it turned out to be CD206, the canonical biomarker for M2-polarized tumor-associated macrophages (TAMs). That made these small proteins really promising as potential drugs, since CD206 is many times more highly expressed on M2 macrophages than on any other somatic cell type."

TAMs are the most common immune cells in the tumor microenvironment, often outnumbering cancer cells themselves in solid tumors. TAMs produce a tumor-promoting tissue environment. Riptide scientists demonstrated that engaging a specific set of amino acids in a particular domain of CD206, returned the macrophage population from M2-dominant to M1-dominant, restoring a tumor-inhibiting microenvironment.

Jaynes’ colleague, Dr. Clayton Yates, Director of Tuskegee’s Cancer Research Center, added, "CD206 is a perfect narrow target for an exquisitely specific therapy. Our team was the first to show that this receptor could serve as a ‘toggle switch’ between macrophage phenotypes. We think it’s accurate to consider it a novel immune checkpoint – a completely natural mechanism that can have a profound effect on tumor etiology, without significant toxicity."

Yates continued, "We demonstrated that both in vitro and in vivo, the RP class of peptides are able to repolarize the macrophage population, and that once repolarized, the macrophages return to phagocytic activity and begin consuming cancer cells. They also send downstream signals to the T-cell, NK-cell and B-cell populations to attack the tumor."

Riptide President Dr. George Martin commented, "The results in animal models of organ cancers have been spectacular. RP-182, administered in combination with gemcitabine, produced the best results ever shown in NCI’s KRAS-p16 pancreatic cancer model. Also, with its distinctive mechanism, it has been shown to powerfully complement both chemotherapy and checkpoint inhibitor immunotherapy."

Dr. Martin continued, "Riptide has built very solid intellectual property around this program, and following the promising early work with RP-182, has developed two other peptide candidates with even better efficacy and excellent pharmacokinetics. These have demonstrated striking results in preclinical models of colon, breast, prostate, and skin cancers."

Riptide Executive Vice President Dr. Henry Lopez added, "Also, since M2 macrophages are important in the progress of certain fibroses, including scleroderma and IPF, we anticipated – and have recently confirmed – potent efficacy in animal models of those diseases."

Dr. Martin concluded, "We’re now engaging with larger pharmaceutical companies to move this important program into clinic. I see a real opportunity, similar in many ways to the discovery of the first checkpoint inhibitors, to make a major impact on clinical practice."

Riptide Bioscience, Inc., with laboratories in Vallejo, California, maintains an intensive program of research into peptide-based therapeutics

On February 13, 2019 Medivir AB reported Year End Report January-December 2019 (Press release, Medivir, FEB 13, 2020, View Source [SID1234554328])

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Preclinical data showing that in addition to its direct effect on cancer cells, MIV-818 also modulates the anti-tumor immune response, presented at the AACR (Free AACR Whitepaper)-NCI-EORTC conference in Boston .
The ninth and final liver cancer patient was included in the phase Ia study with MIV-818. Based on safety and tolerability as well as pharmaco-kinetics and positive biomarker data, it was decided to initiate the phase Ib part of the study.
In December, an investigator-initiated phase II clinical trial of remetinostat was started in patients with squamous cell carcinoma. The study is conducted at the Stanford University School of Medicine in the United States.
The first patient was included in a phase I study evaluating the safety and tolerability of a combination of birinapant and radiation therapy in patients with recurrent Head and Neck Squamous Cell Carcinoma. The study is sponsored and funded as part of the National Cancer Institute’s Cancer Treatment Evaluation Program.
A futility analysis of the phase II combination study with birinapant and Keytruda in colorectal cancer patients was performed. Medivir decided to end the study since the results of the analysis indicated that the study’s goals were unlikely to be achieved.
The first milestone payment for the candidate drug MIV-701 in veterinary medicine was received in October.
Financial summary for the quarter

Net turnover amounted to SEK 1.4 (13.6) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -30.3 (-96.6) million. Basic and diluted earnings per share amounted to SEK -1.32 (-4.72) and SEK -1.32 (-4.72) respectively.
Cash flow from operating activities amounted to SEK -22.6 (-72.4) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 134.6 (286.3) million.
January – December
Financial summary

Net turnover amounted to SEK 8.7 (23.9) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -118.9 (-326.5) million. Basic and diluted earnings per share amounted to SEK -5.08 (-14.62) and SEK -5.08 (-14.62) respectively.
Cash flow from operating activities amounted to SEK -148.5 (-320.5) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 134.6 (286.3) million.
Significant events after the end of the period

The phase II study of MIV-711 in patients with osteoarthritis was published in Annals of Internal Medicine (DOI: 10.7326/M19-0675).
Conference call for investors, analysts and the media
The Year End Report January – December 2020 will be presented by Medivir’s President & CEO, Uli Hacksell.

Time: Thursday, February 13, 2020, at 14.00 (CET).

Phone numbers for participants from:
Sweden +46-8-505-583-52
Europe +44-33-3300-9268
US +1-833-5268-396

The conference call will also be streamed via a link on the website: www.medivir.com
The presentation will be available on Medivir’s website after completion of the conference.
ombined with other medications and exhibits synergistic anticancer activity in preclinical models.

On February 13, 2020 Veracyte, Inc. (Nasdaq: VCYT) reported that Bonnie H. Anderson, chairman and chief executive officer, is scheduled to present at the 9th Annual SVB Leerink Global Healthcare Conference in New York City on Thursday, February 27, 2020 at 10:30 a.m. Eastern Time (Press release, Veracyte, FEB 13, 2020, View Source [SID1234554257]).

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The link to the live audio webcast of the company’s presentation will be available by visiting Veracyte’s website at View Source A replay of the webcast will be available for 90 days following the conclusion of the live presentation broadcast.

On February 13, 2020 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, reported its financial results for the quarter and full year ended December 31, 2019 and reaffirmed its financial guidance for 2020 (Press release, Ultragenyx Pharmaceutical, FEB 13, 2020, View Source [SID1234554297]).

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"In 2019 we created a substantial foundation based on the strong launch of Crysvita and the validation of our gene therapy platform across multiple clinical programs," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "In 2020, we anticipate building on this momentum as we look to the potential approvals of UX007 for LC-FAOD and Crysvita for TIO. We also expect to advance our gene therapy programs into pivotal studies and bring two new programs into the clinic while continuing to exercise financial discipline."

Fourth Quarter and Full Year 2019 Financial Results

Net Revenues
For the fourth quarter of 2019, Ultragenyx reported $35.6 million in total revenue. Ultragenyx recognized $29.9 million in total Crysvita revenue. This includes $26.1 million in collaboration revenue in the North American1 profit share territory and $2.2 million in royalty revenue in the European territory from the collaboration and license agreement with Kyowa Kirin Co., Ltd (KKC). Net product sales for Crysvita in other regions were $1.6 million. Mepsevii (vestronidase alfa) product revenue for the fourth quarter of 2019 was $4.4 million, and UX007 named patient revenue was $1.2 million. Ultragenyx recognized $0.1 million in revenue from its research agreement with Bayer.

Net revenue for the year ended December 31, 2019 totaled $103.7 million. In 2019, Ultragenyx recognized $87.3 million in total Crysvita revenue. This includes $74.9 million in collaboration revenue in the North American1 profit share territory and $8.1 million in royalty revenue in the European territory from the collaboration and license agreement with KKC. Net product sales for Crysvita in other regions totaled $4.3 million. Mepsevii product revenue for the year ended December 31, 2019 was $12.6 million, and UX007 named patient revenue was $3.3 million. Ultragenyx recognized $0.5 million in revenue from its research agreement with Bayer in the year ended December 31, 2019.

Operating Expenses
Total operating expenses for the fourth quarter of 2019 were $130.0 million compared with $106.6 million for the same period in 2018, including non-cash stock-based compensation of $19.7 million and $21.1 million in the fourth quarter of 2019 and 2018, respectively. Total operating expenses for the year ended December 31, 2019, were $527.9 million, which includes $15.6 million in expenditures for Arcturus collaboration and license amendment and $20 million for the upfront payment on the GeneTx agreement, compared with operating expenses of $422.9 million for the same period in 2018. The operating expenses include non-cash stock-based compensation of $82.0 million and $80.1 million in the full year of 2019 and 2018, respectively. The increase in total operating expenses is due to the increase in commercial, development, and general and administrative costs as the company commercializes, grows, and advances its pipeline.

For the fourth quarter of 2019, Ultragenyx reported a net loss of $93.8 million, or $1.62 per share, basic and diluted, compared with a net loss for the fourth quarter of 2018 of $87.8 million, or $1.73 per share, basic and diluted. For the year ended December 31, 2019, the net loss was $402.7 million, or $7.12 per share, basic and diluted, compared with a net loss for the same period in 2018 of $197.6 million, or $3.97 per share, basic and diluted. The loss for the fourth quarter of 2019 and for the year ended December 31, 2019 includes unrealized gains of $1.4 million and $13.4 million, respectively, from the fair value adjustments on the investment in Arcturus equity securities. The loss from the full year 2018 was reduced by the gain on the sale of the Mepsevii priority review voucher (PRV) in January 2018 for net proceeds of $130.0 million and a $40.3 million gain from Ultragenyx’s portion of the sales of the PRV received with the Crysvita approval. The net loss for the full year 2019 reflected cash used in operations of $345.4 million compared to $290.6 million for the same period in 2018.

Cash, Cash Equivalents and Investments
Cash, cash equivalents, and investments were $760.4 million as of December 31, 2019, including proceeds of $320.0 million received from the sale of the company’s royalty interest in Crysvita in the European territory.

2020 Guidance

Crysvita Guidance in Ultragenyx Territories
In 2020, the company continues to expect Crysvita revenue in the Ultragenyx territories to be between $125 million and $140 million, which excludes the European territory revenue. Ultragenyx territories include the collaboration revenue from the North American profit share territory (US and Canada) and other regions where revenue from product sales are recognized by Ultragenyx (Latin America, Turkey). In December 2019, the European territory royalty revenue rights were sold to Royalty Pharma. As a result, the company will no longer receive cash payments from the EU territory royalty revenue rights beginning January 1, 2020, until the respective threshold amount is met; however, the company will continue to record the royalty as "non-cash" revenue.

2020 Expected Net Cash Burn Rate
The company also expects a more than 20 percent reduction in net cash burn (net cash used in operations plus capital expenditures) in 2020 compared to 2019 due to a combination of financial discipline in spending with flattening operating expense growth, combined with the significantly larger growth in revenue.

Recent Updates and Upcoming Milestones

Crysvita for X-linked Hypophosphatemia: Non-dilutive $320 million sale of future European royalties

In December 2019, Ultragenyx sold to Royalty Pharma for $320 million its royalty interest in Crysvita in the European territory, where it is being commercialized by Kyowa Kirin Co., Ltd.
Crysvita for Tumor-Induced Osteomalacia (TIO): Supplemental Biologics License Application (sBLA) submitted

Ultragenyx submitted the sBLA to the U.S. FDA on December 18, 2019 and expects to hear back from FDA on submission acceptance and review designation in February 2020.
UX007 for Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD): NDA under review by U.S. FDA

The U.S. FDA accepted for review the New Drug Application (NDA) and has set a Prescription Drug User Fee Act (PDUFA) date of July 31, 2020. The FDA has indicated that it is not currently planning to hold an advisory committee meeting to discuss the application. The review process is on track for a decision by the PDUFA date.
DTX301 for Ornithine Transcarbamylase (OTC) Deficiency: Positive data from higher dose cohort of Phase 1/2 study; data from prophylactic steroid cohort in second half 2020

Recent positive data from Cohort 3 indicated two confirmed responders and a potential third responder out of three total patients, as well as a new responder in Cohort 2. There are currently up to six responders of the nine dosed to date with a more consistent response at higher doses.
Ultragenyx is initiating a fourth cohort (n=3) using prophylactic steroids at the same dose as Cohort 3. Data from the prophylactic steroid cohort are expected in the second half of 2020.
DTX401 for Glycogen Storage Disease Type Ia (GSDIa): Positive data from Phase 1/2 study; enrollment complete in confirmatory cohort and data expected in first half 2020

Enrollment is complete in the confirmatory cohort of three patients at the second dose cohort, with data expected in the first half of 2020. Following the results of the confirmatory cohort, a Phase 3 study could begin in the second half of 2020.
GTX-102 for Angelman Syndrome (AS): Partnered program with GeneTx; IND active and enrollment of first patient expected in first half 2020

An investigational new drug (IND) application is now active and GeneTx has received Institutional Review Board (IRB) approval from the first study site. Enrollment in the Phase 1/2 study of GTX-102 is expected to begin in the first half of 2020.
In February 2020, Ultragenyx paid $25 million after the acceptance of the IND to maintain its option to acquire GeneTx until the earlier of 30 months from the first dosing of a patient in the Phase 1/2 study (subject to extensions) or 90 days after results are available from that study.
UX701 for Wilson Disease: IND expected by the end of the year

An IND application is expected by the end of 2020 for a new gene therapy for Wilson disease, a larger rare metabolic disease. UX701 will be the company’s second clinical program to utilize its HeLa manufacturing system.
DTX201 / BAY 2599023 for Hemophilia A: Partnered with Bayer; Cohort 2 data presented at European Association for Haemophilia and Allied Disorders (EAHAD)

Three cohorts with two patients each, six patients in total, have been dosed with AAVhu37 (DTX201 / BAY 2599023), using material from Ultragenyx’s proprietary HeLa manufacturing platform. Longer term dose cohort 1 and new dose cohort 2 data presented at EAHAD showed three of four patients have achieved clinically meaningful FVIII levels. One patient in Cohort 1 has achieved clinically meaningful FVIII levels and has experienced four bleeds since receiving treatment down from 99 bleeds the prior year. Both patients in dose cohort 2 achieved clinically meaningful FVIII levels out to 24 and 30 weeks. Patient 4 has been off treatment and bleed free for seven months as of the data cut-off date. The second patient in dose cohort 2 had mild ALT/AST elevations that was managed with a short tapering course of corticosteroids.
Conference Call and Webcast Information

Ultragenyx will host a conference call today, Thursday, February 13, 2020, at 2 p.m. PT/ 5 p.m. ET to discuss fourth quarter and full year 2019 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 5068548. The replay of the call will be available for one year.