FluMist Flopped for Kids During Recent Flu Seasons

Live attenuated influenza vaccine (LAIV4), or FluMist, was less effective at preventing flu, especially influenza A/H1N1, in recent flu seasons among kids than inactivated influenza vaccine (IIV) was, researchers found.

A pooled analysis found that vaccine effectiveness for quadrivalent live attenuated influenza vaccine among children was 20% (95% CI -6% to 39%) for children ages 2-17 against influenza A/H1N1 (pdm09) compared with 67% (95% CI 62%-72%) for the inactivated influenza vaccine, reported Jessie Chung, MPH, of the CDC, and colleagues.

Moreover, patients who received LAIV4 had significantly higher odds of contracting the H1N1 strain compared with those who received IIV (OR 2.66, 95% CI 2.06-3.44), the authors wrote in Pediatrics.

When combining data from the 2013-2014 to the 2015-2016 flu seasons, overall vaccine effectiveness against any flu was 26% (95% CI 15%-36%) for LAIV4 compared with 51% (95% CI 47%-54%) for IIV, and recipients of LAIV4 had higher odds of testing positive for any flu (OR 1.48, 95% CI 1.28-1.70), they noted.

FluMist has had a roller coaster of highs and lows in recent years — going from the CDC’s Advisory Committee on Immunization Practices (ACIP) giving a preferential recommendation to this type of vaccine during the 2014-2015 season, to kicking it off the roster entirely during the 2016-2017 flu season, to adding it back as an option during the 2018-2019 flu season.

Regardless, the American Academy of Pediatrics (AAP) recently encouraged clinicians to use inactivated influenza vaccine as the “primary choice” when possible, and AAP liaison members spoke out against reinstating FluMist at the February 2018 ACIP meeting.

In this study, the authors raised questions about the accuracy of prior LAIV4 vaccine efficacy estimates, citing “heterogeneous findings,” as well as potential differences between U.S. and European vaccine effectiveness, where prior vaccination in the U.S. may have had an impact.

Researchers examined pooled individual patient-level data from five studies ranging from 2013-2014 to 2015-2016 in the CDC’s U.S. Influenza Vaccine Effectiveness Network.

Overall, data from over 17,000 children ages 2-17 was included, with an average age of around 7. One-fourth of patients tested positive for influenza, and among them 37% were infected with influenza A/H3N2, with 25% infected with influenza A/H1N1 (pdm09), and 25% infected with influenza B.

One third of patients were vaccinated and 30% of those received quadrivalent live attenuated influenza vaccine, the authors said. The authors noted that LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B viruses.

An accompanying editorial by Pedro Piedra, MD, of Baylor College of Medicine in Houston, said that the results of these five combined observational studies “provide a compelling argument why ACIP made the interim recommendation against… use” of LAIV4 in two recent flu seasons.

Piedra also reviewed potential hypotheses from the World Health Organization, including “methodological study differences; inadequate vaccine handling at vaccine distribution centers; intrinsic virological characteristics of the novel A/H1N1pdm09… used in the initial formulations of LAIV4.”

Other considerations included improved coverage across age groups since the ACIP made a universal influenza vaccine recommendation in 2010 and potential “viral interference” from the second B strain when the vaccine changed from a trivalent to a quadrivalent during the 2013-2014 season, Piedra said.

He cited an interim analysis on vaccine effectiveness from England, which found an interim end-of-season adjusted vaccine effectiveness for LAIV4 in children ages 2-17 of 90.3% (95% CI 16.4%-98.9%) against influenza A/H1N1 (pdm09) for the 2017-2018 season. Piedra characterized this result as “encouraging.”

Limitations to the data cited by Chung and colleagues, they said, included that “descriptive patient information beyond age, sex, and geographic region of enrollment” was not available for all studies, which could result in unmeasured confounding. The authors also said that historical vaccination data was limited to the season prior to enrollment as opposed to an entire vaccination history for most patients.

The study was supported by the National Institutes of Health (NIH).

The U.S. Influenza Vaccine Effectiveness Network was supported by the Centers for Disease Control and Prevention, the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, the University of Pittsburgh, Baylor Scott & White Health (U01 IP000473), and the NIH.

The Influenza Clinical Investigation for Children was supported by MedImmune.

Chung disclosed no conflicts of interest; other co-authors disclosed being employees of AstraZeneca.

Piedra disclosed support from AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, Merck Sharp and Dohme, and Seqirus.

LAST UPDATED 01.04.2019

• Primary Source

  Pediatrics

  Source Reference: Chung JR “Live attenuated and inactivated influenza vaccine effectiveness” Pediatrics 2019; DOI: 10.1542/peds.2018-2094.

• Secondary Source

  Pediatrics

  Source Reference: Piedra PA “Live attenuated influenza vaccine: Will the phoenix rise again?” Pediatrics 2019; DOI: 10.1542/peds.2018-3290.

https://www.medpagetoday.com/pediatrics/vaccines/77269

Ultragenyx’s DTX401 shows positive action in glycogen storage disease

Ultragenyx Pharmaceutical (NASDAQ:RARE) is up 4% premarket, albeit on only 100 shares, following its announcement of preliminary data from a Phase 1/2 trial evaluating gene therapy DTX401 in patients with glycogen storage disease type Ia, an inherited disorder characterized by the build up of sugar (glycogen) in cells leading to impaired organ function.

Three patients in the lowest dose cohort all experienced improved glucose control and increased time to hypoglycemia (low blood sugar) during fasting while two experienced clinically meaningful improvements in time to hypoglycemia during a controlled fasting challenge.

No infusion-related adverse events and no serious treatment-related adverse events have been reported. All adverse events to date have been mild or moderate.

Enrollment is the second cohort will begin this month with interim data expected mid-year.

https://seekingalpha.com/news/3420658-ultragenyxs-dtx401-shows-positive-action-glycogen-storage-disease-shares-4-percent-premarket

Top 20 Life Science Startups to Watch in 2019

BioSpace is proud to present its NextGen Bio “Class of 2019,” a list of 20 up-and-coming life science companies in North America that launched* no earlier than 2017.

The NextGen Bio Class of 2019 is a stellar group of companies that are already making an enormous impact on the industry now and will continue into the future. Congratulations to this group!

RANK	COMPANY	LAUNCHED	LOCATION	POINTS
1	Allogene Therapeutics	2018	California	59
2	Gossamer Bio	2018	California	41
3	Viela Bio	2018	Maryland	33
4	SpringWorks Therapeutics	2017	New York	28
5	NanOlogy	2017	Texas	19
6	Cullinan Oncology	2017	Massachusetts	18
7	Ambys Medicines	2018	California	18
8	Skyhawk Therapeutics	2018	Massachusetts	17
9	The Bill & Melinda Gates Medical Research Institute (MRI)	2018	Massachusetts	17
10	Ansun Biopharma	2018	California	16
11	Magnolia Neurosciences	218	New York	16
12	Compass Therapeutics	2018	Massachusetts	15
13	Beam Therapeutics	2018	Massachusetts	15
14	Joyn Bio	2018	Massachusetts	14
15	Partner Therapeutics	2018	Massachusetts	14
16	DataVant	2017	California	13
17	Genevant Sciences	2018	Massachusetts	13
18	Akouos	2018	Massachusetts	12
19	Akero Therapeutics	2018	Massachusetts / California	12
20	Rheos Medicines, Inc.	2018	Massachusetts	11

1. Allogene Therapeutics

Points: 59
Launched: 2018
Location: South San Francisco, CA
Notable:
• Allogene closed a $300 million Series A venture round in April 2018, which included investments from Pfizer and Gilead Sciences.
• The company is focused on developing off-the-shelf CAR-T products.
• Allogene has access to 16 preclinical CAR-T licenses that Pfizer licensed from Cellectis and Servier.
• One of the licensed assets, UCART19, is expected to begin Phase II clinical trials in 2019.
• The company completed a $120 million private financing of convertible notes.
• Allogene raised $324 million in IPO, second highest IPO behind Moderna.
• Pfizer has a 25 percent stake in Allogene.

2. Gossamer Bio

Points: 41
Launched: 2018
Location: San Diego, CA
Notable:
• Gossamer Bio launched in January 2018 with a $100 million Series A financing, which was followed in July by a $230 million Series B financing.
• Gossamer Bio focuses on immunology and fibrosis, inflammation and immuno-oncology.
• The company currently has two products in Phase I clinical trials, two in Phase II, and two in preclinical studies.

3. Viela Bio

Points: 33
Launched: 2018
Location: Gaithersburg, MD
Notable:
• Viela Bio spun out of MedImmune in 2018.
• In February 2018, the company closed a Series A financing worth $282.3 million.
• Viela Bio focuses on severe inflammation and autoimmune diseases by targeting shared critical pathways.
• The company launched with three clinical and three pre-clinical drugs from MedImmune. These drugs include inebilizumab which is currently in Phase II for neuromyelitis optica, a rare condition of the optic nerve and spinal cord.

4. SpringWorks Therapeutics

Points: 28
Launched: 2017
Location: New York, NY
Notable:
• SpringWorks Therapeutics launched with a $103 million Series A round, with Bain Capital, OrbiMed, and Pfizer as investors.
• SpringWorks holds the rights to four clinical-stage therapies from Pfizer.
• SpringWorks has partnerships in place with Desmoid Tumor Research Foundation, Children’s Tumor Foundation, Cohen Veterans Bioscience, University of California David, Boston Children’s Hospital, the Alzheimer’s Drug Discovery Foundation and BeiGene.
• The company’s most advanced drug candidate, nirogacestat, received orphan drug designation from the U.S. Food and Drug Administration (FDA) for desmoid tumors and PD-0325901 received orphan drug designation from the FDA for neurofibromatosis type 1.

5. NanOlogy

Points: 19
Launched: 2017
Location: Fort Worth, TX
Notable:
• NanOlogy was formed by DFB Pharmaceuticals, CritiTech, and US Biotest with seed funding of $2 million.
• NanOlogy is focused on developing naked nanoparticle forms of paclitaxel and docetaxel for local delivery of the therapeutics to treat cancer and other diseases.
• The company is currently running Phase I trials for prostate cancer, pancreatic cancer, pancreatic mucinous cysts and others.

6. Cullinan Oncology

Points: 18
Launched: 2017
Location: Cambridge, MA
Notable:
• Cullinan Oncology launched in October 2017 with a Series A financing worth $150 million.
• Cullinan is developing a venture fund/biotech business model where it plans to have 8 to 12 drugs in development with each drug having a dedicated chief executive. But instead of having a research team for each drug, Cullinan scientists will share company resources.
• Cullinan has three assets in its pipeline with one licensed from an unidentified university.
• The company signed a collaboration deal with MAB Discovery GmbH in February 2018.

7. Ambys Medicines

Points: 18
Launched: 2018
Location: Redwood City, CA
Notable:
• Ambys launched in August 2018 in a Series A financing round worth $60 million, funded by Third Rock Ventures and Takeda.
• As part of the launch, Ambys signed a strategic partnership with Takeda with an additional $80 million commitment to fund research.
• Ambys will focus on chronic liver disease, including cell therapy for hepatocyte transplantation, gene therapy for liver regeneration, and drug therapy to replace lost protein function.

8. Skyhawk Therapeutics

Points: 17
Launched: 2018
Location: Waltham, MA
Notable:
• In June 2018, Skyhawk Therapeutics closed a $40 million equity investment round and then, in an unusual deal, signed a five-year collaborative agreement with Celgene that included an upfront $60 million.
• Skyhawk focuses on developing small molecule therapeutics that correct RNA mis-splicing, what is usually called exon skipping.
• The company expects to move its first oncology treatment into the clinic in 2019.
• Skyhawk currently has four targets in oncology and three in neuro, which are in lead selection but past preclinical IND filing.

9. The Bill & Melinda Gates Medical Research Institute (MRI)

Points: 17
Launched: 2018
Location: Cambridge, MA
Notable:
• In 2018, The Bill & Melinda Gates Foundation decided to launch a biotech company named The Bill & Melinda Gates Medical Research Institute (MRI).
• MRI will focus on vaccines, especially malaria, tuberculosis and enteric diseases.
• The company expects to work with academic laboratories and biotech firms to shepherd programs through the early-to-middle stage of development then hunt for commercial partners.
• Via the Foundation, MRI has an annual operating budget of $100 million.
• MRI’s lead project is determining if the well-documented BCG vaccine given to adolescents can increase their resistance to tuberculosis.

10. Ansun Biopharma

Points: 16
Launched: 2018
Location: San Diego, CA
Notable:
• Ansun Biopharma launched on May 14, 2018, with $85 million in Series A financing from Sinopharm Healthcare Fund and Lilly Asia Ventures. Additional new investors include Lyfe Capital, Yuanming Capital, Matrix Partners China, 3e Bioventures Capital, Oceanpine Capital, VI Ventures and Joincap Investment.
• The company has two products in Phase II clinical trials: 1) Fludase is a first-in-class therapeutic to treat all forms of influenza; 2) Paradase is a nebulized drug for parainfluenza viruses.

11. Magnolia Neurosciences

Points: 16
Launched: 2018
Location: New York, NY
Notable:
• Magnolia Neurosciences Corporation was co-founded by Accelerator Life Science Partners and The University of Texas MD Anderson Cancer Center.
• The company launched in August 2018 with a $31 million Series A financing, which included AbbVie Ventures, Alexandria Venture Investments, ARCH Venture Partners, Eli Lilly and Co., Innovative NY Fund, Johnson & Johnson Innovation – JJDC, Inc., the Partnership Fund for New York City, Pfizer Ventures, Watson Fund, and WuXi, AppTec’s Corporate Venture Fund and 180 Degree Capital Corp.
• The company’s subsidiary, Korysso Therapeutics, received a $19.95 million grant from the Cancer Prevention and Research Institute of Texas in August 2018.

12. Compass Therapeutics

Points: 15
Launched: 2018
Location: Cambridge, MA
Notable:
• Launched with the final $49 million of a $132 million Series A financing in July 2018, led by OrbiMed Advisors and included F-Prime Capital, Cowen Healthcare Investment, Thiel Capital, Biomatics Capital, Ulysses Holdings, Borealis Ventures, Alexandria Ventures Investments and Biomed Realty Ventures.
• Currently has 15 therapeutic candidates advancing through preclinical programs for cancer, inflammation and autoimmune diseases.

13. Beam Therapeutics

Points: 15
Launched: 2018
Location: Cambridge, MA
Notable:
• Beam Therapeutics launched with up to $87 million in cumulative Series A funding led by F-Prime Capital Partners and ARCH Venture Partners in May 2018.
• Beam focuses on multiple DNA base editor platforms developed in the lab of David Liu and the RNA base editor platform developed by Feng Zhang at the Broad Institute of MIT and Harvard.
• The company has licensed tech from Harvard for two base editing platforms.
• Beam entered into a licensing and option agreement with Editas Medicine.

14. Joyn Bio

Points: 14
Launched: 2018
Location: Boston, MA
Notable:
• Joyn Bio is a joint venture between Bayer AG and Ginkgo Bioworks.
• Joyn Bio was launched with a $100 million Series A financing led by Bayer, Ginkgo BIoworks and Viking Global Investors.
• In addition to the financing, Ginkgo is offering Joyn access to technology, laboratory and office space, and is building a new facility just for Joyn.
• Bayer is providing access to proprietary microbial strains.
• Joyn Bio is focused on synthetic biology for agricultural applications.

15. Partner Therapeutics

Points: 14
Launched: 2018
Location: Lexington, MA
Notable:
• Partner Therapeutics launched in February 2018 with a $60 million Series A financing led by Perceptive Advisors, Adams St. Partners and MidCap Financial.
• The company acquired rights to Leukine (sargramostim) from Sanofi in February 2018, which was already approved, and will develop the drug for new indications.
• Partner Therapeutics signed a distribution deal with Tanner Pharmaceuticals for Leukine in May 2018.
•  In June, the FDA approved Leukine for the treatment of acute radiation syndrome and in November Leukine was granted orphan drug designation for pulmonary alveolar proteinosis.

16. Datavant

Points: 13
Launched: 2017
Location: San Francisco, CA
Notable:
• Datavant is a part of Roivant Sciences, one of Vivek Ramaswamy’s numerous companies.
• The company focuses on utilizing artificial intelligence to improve the clinical trial process and is led by Travis May, a Silicon Valley tech veteran who was co-founder and chief executive officer of LiveRamp.
• Datavant had a $40 million financing round in April 2018 led by Roivant Sciences and Travis May.
• In April 2018, Datavant acquired Universal Patient Key (UPK), a leading provider of HIPAA-compliant de-identification services for healthcare data.
• In May 2018, Datavant teamed with Worldwide Clinical Trials, a Contract Research Organization (CRO).

17. Genevant Sciences

Points: 13
Launched: 2018
Location: Cambridge, MA
Notable:
• Genevant is one of Vivek Ramaswamy’s companies under the umbrella of Roivant Sciences.
• Genevant was formed by Arbutus Biopharma Corporation and Roivant Sciences as a jointly-operated company focused on discovery, development, and commercialization of RNA-based therapeutics enabled by Arbutus’ proprietary nanoparticle (LNP) and ligand conjugate delivery technologies.
• Roivant had a $116 million stake in Arbutus’ hepatitis B program.
• Genevant was launched with $37.5 million in seed capital from Roivant.
• Genevant signed a research deal with BioNTech to develop five products for rare diseases.

18. Akouos

Points: 12
Launched: 2018
Location: Boston, MA
Notable:
• Launched in 2018 with a $50 million Series A co-led by 5AM Ventures and New Enterprise Associates, who were joined by existing seed investor Partners Innovation Fund and new investors Sofinnova Ventures, RA Capital Management and Novartis Venture Fund.
• The company will focus on developing AAV-based gene therapies for sensorineural hearing loss.
• The company has licensed technology from Massachusetts Eye and Ear, and Lonza.

19. Akero Therapeutics

Points: 12
Launched: 2018
Location: Cambridge, MA / San Francisco, CA
Notable:
• Akero Therapeutics launched in June 2018 with a $65 million Series A co-led by Apple Tree Partners, Atlas Venture, venBio Partners and Versant Ventures and most recently, closed $70 million Series B in December.
• The company’s focus is on non-alcoholic steatohepatitis (NASH) and other serious metabolic diseases.
• Akero’s lead clinical program is AKR-001, a long-acting fibroblast growth factor 21 (FGF21) analogue, which it licensed from Amgen and plans to initiate a Phase II clinical trial in NASH.

20. Rheos Medicines, Inc.

Points: 11
Launched: 2018
Location: Cambridge, MA
Notable:
• Rheos Medicines launched in March 2018 with a $60 million Series A financing backed by Third Rock Ventures.
• The company focuses on developing therapies for immune-mediated diseases by tuning metabolic pathways in immune cells.
• Rheos Medicines’ product engine is a proprietary Immune Cell Encyclopedia (ICE), which maps the metabolic pathways by using different types of immune cells to regulate their fate and function.

To come up with this Top 20, BioSpace sorted companies into that age grouping, and they were then weighted by a number of different categories and finally ranked in a cumulative fashion, based on the points awarded for each category. These categories were: Finance, Collaborations, Pipeline and Innovation.

https://www.biospace.com/article/1-top-20-life-science-startups-to-watch-in-2019/

Curaleaf Opens New Medical Cannabis Dispensary In New York

U.S. cannabis retailer Curaleaf Holdings (CSE: CURA) (OTCBB: CURLF) has opened its fourth dispensary in New York State, bringing the total number of the company’s dispensaries to 36.

Located at 255 Glen Cove Road in Carle Place, Long Island, the new location offers medical cannabis patients in Nassau and Suffolk counties easier and more convenient access to product, the company said in a press statement.

New Curaleaf Cannabis Location

According to Curaleaf, the new Carle Place location will offer a range of free wellness and medical marijuana educational programs such as health seminars led by medical professionals and yoga classes. The company plans to support local community events and initiatives such as the Susan G. Komen annual “Race For The Cure,” EPIC Long Island, and the Multiple Sclerosis Society of NY and Long Island.

“This new location will serve a community of patients in Long Island and provide them with high-quality medical cannabis used to help patients suffering from chronic pain, cancer, opioid addiction, PTSD and other ailments,” Curaleaf New York President Michelle Bodner said in the statement.

The dispensary’s operating hours are Tuesday through Thursday and Saturday, 10:30am – 6pm; Friday, 11:30am -7pm; closed on Sundays and Mondays. Throughout the year, discounts are offered to military veterans and recipients of Medicaid.

Curaleaf recently expanded its product line by adding new products and nine new SKU’s – Curaleaf Slim Vape Pen, Peppermint Flavored Tincture, and Lemon Flavored Tinctures. The company says that it made these products from cannabis grown in the state and processed at the company’s cultivation facility in Ravena, New York.

Curaleaf also operates medical cannabis dispensaries in Newburgh, Plattsburgh and Forest Hills, Queens.

The State of New York does not allow cannabis for recreational use. However, it is legal to use cannabis for medical purposes, while possession of small amounts is decriminalized in the state.

https://www.marketscreener.com/CURALEAF-HOLDINGS-INC-46901467/news/Curaleaf-Opens-New-Medical-Cannabis-Dispensary-In-New-York-27829508/

Mesoblast Phase 3 Trial of Heart Failure Cell Therapy Completes Recruitment

Mesoblast Limited (ASX:MSB; Nasdaq:MESO), world leader in development and commercialization of allogeneic (off-the-shelf) cellular medicines, today announced that it has completed patient recruitment in the events-driven Phase 3 trial of its product candidate Revascor (MPC-150-IM) for advanced chronic heart failure.

Mesoblast Chief Executive Dr Silviu Itescu stated: “Completion of recruitment in this Phase 3 trial, the largest cell therapy trial for heart failure, is a key milestone for Mesoblast and has been achieved on plan. This is a substantial step forward in our objective to bring an effective therapy to countless patients with progressive heart failure, and a tremendous commercial opportunity for Mesoblast.”

The Phase 3 trial is evaluating whether Revascor reduces recurrent non-fatal heart failure-related major adverse cardiac events (HF-MACE), and prevents or delays terminal cardiac events (TCEs), defined as cardiovascular death, heart transplant or placement of an artificial device, over at least 12 months. In a previous Phase 2 trial, a single dose of Revascor prevented any TCEs or hospitalization events over three years in a similar patient cohort.

The Phase 3 trial has enrolled approximately 570 patients across 55 centers in North America. This enrollment target was guided by the observed reduction in event rate in the Phase 2 trial and reinforced by the successful outcome of a pre-specified futility analysis of the Phase 3 trial’s primary endpoint performed after the first 270 patients were enrolled.

The trial’s co-principal investigator, Dr Emerson Perin, Medical Director of Texas Heart Institute and Director of its Stem Cell Center, said: “We are very pleased to have completed recruitment in this important trial of a cellular therapy for advanced heart failure patients who have few alternatives. If the Phase 3 trial results confirm the earlier Phase 2 data, where we saw improvements in patient function as well as reductions in hospitalizations and deaths, this important technology will transform cardiovascular care and would provide a powerful new treatment for advanced heart failure.”

There are over 8 million patients with heart failure in the United States alone, with 15-20% refractory to all existing medicines and progressing to advanced heart failure1(New York Heart Association Class III or IV). These patients represent a major unmet medical need due to their high rates of HF-MACE events and mortality.

Dr Itescu added: “Over the past 12 months, Mesoblast has completed recruitment in all three of its Phase 3 trials, for acute graft versus host disease, chronic low back pain, and now chronic heart failure.”

https://www.marketscreener.com/MESOBLAST-LIMITED-6499027/news/Mesoblast-P3-Trial-of-MSB-s-Cell-Therapy-in-CHF-Completes-Recruitment-27829642/

Adverum Biotechnologies Provides 2019 Outlook

Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ophthalmology and rare diseases, today reviewed recent progress and provided an outlook for 2019.

“For our lead gene therapy ADVM-022 for the treatment of wet AMD, we are building off of last year’s momentum to execute our ongoing OPTIC phase 1 clinical trial,” said Leone Patterson, chief executive officer of Adverum Biotechnologies. “In a very short period, we have dosed our first patient in the OPTIC phase 1 trial, published long-term preclinical efficacy data in a leading scientific journal, and received Fast Track designation for ADVM-022. With this key groundwork complete, this year our primary focus is on advancing this gene therapy for an initial indication in wet AMD and evaluating additional anti-VEGF indications to pursue. We have sufficient cash to fund operations at least through the first half of 2020, including interim data from the three cohorts in the OPTIC trial. Our team is excited to be working on developing this novel single intravitreal injection therapy for patients.”

Key Accomplishments for 2018

	•	In December 2018, long-term preclinical expression and efficacy data on ADVM-022 in wet age-related macular degeneration (wet AMD) were published in Molecular Therapy, a leading peer-reviewed scientific journal. The data in this publication combined with two year preclinical expression data presented in October 2018 at the European Society of Gene and Cell Therapy (ESGCT) showed the following:
		A single intravitreal injection of ADVM-022 in non-human primates (NHPs) at dose ranges of 2 x 10 11 vg/eye to 2 x 10 12 vg/eye provided stable intraocular expression of aflibercept at levels comparable with the levels measured in aflibercept recombinant protein-injected eyes approximately 3 to 4 weeks post-dose in all of the following: vitreous humor, aqueous humor, retina and choroid A single intravitreal injection of ADVM-022 provided robust and durable expression of aflibercept, sustained for approximately two years post-dose in NHPs In a laser-induced choroidal neovascularization model in NHPs, a single intravitreal injection of ADVM-022 13 months before lasering prevented the occurrence of clinically relevant choroidal neovascularization lesions, similar to animals that received a bolus of intravitreal aflibercept (standard-of-care) at the time of lesioning A single intravitreal injection of ADVM-022 delivering a continuous supply of aflibercept may provide an effective long-term treatment option and prevent further vision loss for patients with wet AMD The full online publication can be accessed at the following link: https://doi.org/10.1016/j.ymthe.2018.11.003.
	•	In November 2018, Adverum dosed the first patient in the OPTIC phase 1 trial evaluating a single intravitreal injection of ADVM-022 for patients with wet AMD. ADVM-022 (AAV.7m8-aflibercept) is designed to provide long-lasting therapy without the need of chronic or frequent anti-VEGF injections
	•	In September 2018, Adverum received Fast Track designation for ADVM-022 in wet AMD from the U.S. Food and Drug Administration (FDA). Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Despite the availability of anti-VEGF therapies, patients with wet AMD still have a significant burden from the frequency of injections and undertreatment may lead to vision loss
	•	In late August 2018, Adverum announced that the IND application for ADVM-022 in patients went active

2019 Outlook – Planned Pipeline MilestonesADVM-022 for wet AMD

• Provide an update on enrollment from the OPTIC phase 1 clinical trial in the first half of 2019
• Provide interim data on the three cohorts from the OPTIC phase 1 clinical trial by the first quarter of 2020

Rare Disease Program

• Provide an update on rare disease program’s preclinical development plan in the first half of 2019

Financial Guidance
Adverum’s cash, cash equivalents and marketable securities were $217.9 million as of September 30, 2018. Adverum expects this quarter-end cash position to fund operations at least through the first half of 2020.

Upcoming Events

	•	Adverum plans to participate in the following upcoming conferences:
		J.P. Morgan’s 37th Annual Healthcare Conference in San Francisco January 7-10, 2019. CEO Leone Patterson will present on Thursday, January 10 at 8:00 am PT Leerink’s 8th Annual Global Healthcare Conference in New York, February 27-March 1, 2019 Cowen’s 39th Annual Health Care Conference in Boston, March 11-13, 2019

https://www.marketscreener.com/ADVERUM-BIOTECHNOLOGIES-I-27535811/news/Adverum-Biotechnologies-Provides-2019-Outlook-27829690/

Xenon Pharmaceuticals Outlines 2019 Key Milestones

Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a clinical stage biopharmaceutical company, today provided a corporate update and outlined its anticipated key milestone events in 2019.

Dr. Simon Pimstone, Xenon’s Chief Executive Officer, said, “Xenon is entering 2019 in a strong position, poised to support multiple neurology programs that are expected to be in Phase 2 or later stage development this year. With four distinct therapeutic candidates – XEN496, XEN1101, XEN901 and XEN007 – that are aimed at treating neurological disorders, including epilepsy, we intend to pursue a variety of development strategies, such as those focused on using a ‘precision medicine’ approach to address rare pediatric disorders including KCNQ2 epilepsy as well as those targeting broader patient populations, including adult patients with focal epilepsy. During 2019, we expect to advance our ongoing XEN1101 Phase 2b clinical trial in adult focal epilepsy, initiate a Phase 3 clinical trial for XEN496 for the treatment of KCNQ2 epilepsy, and initiate a Phase 2 clinical trial for XEN901 in either a pediatric or adult epilepsy indication based on regulatory feedback. In addition, we expect to initiate at least one Phase 2 clinical trial for XEN007 in an orphan neurological indication and continue our drug discovery efforts to identify new therapeutic candidates.”

Anticipated Milestones

• XEN496 (active ingredient ezogabine) is a Kv7 potassium channel modulator being developed for the treatment of KCNQ2 epileptic encephalopathy (KCNQ2-EE). Ezogabine was previously approved by the U.S. Food and Drug Administration (FDA), as an anti-epileptic drug (AED) as an adjunctive treatment for adults with focal seizures with or without secondary generalization. Xenon received orphan drug designation (ODD) from the FDA for XEN496 as a treatment of KCNQ2-EE. A steering committee made up of key opinion leaders in the KCNQ2-EE and pediatric epilepsy fields has been established to help guide the clinical development of XEN496. In response to Xenon’s pre-IND briefing package submission, the FDA indicated that it was acceptable to study XEN496 in infants and children up to 4 years old, and that a single pivotal trial in approximately 20 patients may be considered adequate in order to demonstrate XEN496’s efficacy in KCNQ2-EE. Xenon is currently finalizing a pediatric-specific formulation to complete pre-clinical formulation testing with a final drug product expected in the second quarter of 2019. Xenon expects to file an Investigational New Drug (IND) application in the third quarter of 2019, and, based on regulatory feedback, Xenon expects to initiate a Phase 3 clinical trial thereafter.
• XEN1101 is a Kv7 potassium channel modulator being developed for the treatment of epilepsy and potentially other neurological disorders. Xenon announced final data from its XEN1101 Phase 1 clinical trial and the related transcranial magnetic stimulation (TMS) studies at the American Epilepsy Society (AES) Annual Meeting in December 2018. Based on the encouraging Phase 1 data and TMS results, Xenon has initiated a Phase 2b clinical trial in adult patients with focal epilepsy. A Clinical Trial Application (CTA) has been accepted by Health Canada enabling the start of patient screening, and the first patient in the XEN1101 Phase 2b clinical trial is expected to be enrolled in the near term. Xenon has also submitted regulatory filings to support the clinical development of XEN1101 in other jurisdictions, including the United States and Europe. The XEN1101 Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled, multicenter study to evaluate the clinical efficacy, safety and tolerability of XEN1101 administered as adjunctive treatment in adult patients with focal epilepsy. Approximately 300 patients will be randomized in a blinded manner to one of three active treatment groups or placebo in a 2:1:1:2 fashion (XEN1101 25 mg : 20 mg : 10 mg : Placebo). The primary endpoint is the median percent change in monthly focal seizure frequency from baseline compared to treatment period of active versus placebo. Depending upon the rate of enrollment, top-line results from the XEN1101 Phase 2 clinical trial are anticipated in the second half of 2020.
• XEN901 is a potent, highly selective Nav1.6 sodium channel inhibitor being developed for the treatment of epilepsy. Xenon announced interim results from its XEN901 Phase 1 clinical trial and the related pilot TMS study at the AES Annual Meeting in December 2018. The next steps for XEN901 include completing the Phase 1 clinical trial and continued planning for Phase 2 clinical development evaluating XEN901 as a treatment for adult focal seizures or for rare, pediatric forms of epilepsy, including SCN8A gain-of-function epilepsy patients, depending on feedback from planned discussions with regulatory agencies. Xenon expects to receive regulatory feedback on advancing XEN901 directly into pediatric SCN8A gain-of-function epilepsy patients in the second quarter of 2019, and pediatric formulation development and juvenile toxicology studies are underway.
• XEN007 (active ingredient flunarizine) is a CNS-acting calcium channel inhibitor that directly modulates the Cav2.1 channel. Flunarizine has been used outside of the U.S. in the prevention of chronic migraine, and in case studies, it has been reported to have clinical benefit in other neurological disorders, including hemiplegic migraine (HM) and alternating hemiplegia of childhood (AHC). Xenon has received ODD from the FDA for XEN007 for the treatment of HM and AHC. In addition, Xenon entered into key agreements in order to access regulatory files and manufacturing support to potentially enable an accelerated clinical development of XEN007 directly into a Phase 2 clinical trial. Xenon is currently evaluating various development strategies for XEN007, including the support of at least one Phase 2 clinical trial in an orphan neurological indication.
• As of September 30, 2018, cash and cash equivalents and marketable securities were $127.1 million. Based on current assumptions, which include fully supporting the planned clinical development of XEN496, XEN1101, XEN901 and XEN007, Xenon anticipates having sufficient cash to fund operations into 2021, excluding any revenue generated from existing partnerships or potential new partnering arrangements.

https://www.marketscreener.com/XENON-PHARMACEUTICALS-INC-18411162/news/Xenon-Pharmaceuticals-Outlines-2019-Key-Milestones-27829731/