Category Archives: Genetic Medicine

Another component of more regular monitoring is using sensors for continuous, remote evaluation of blood pressure, breathing, body temperature and other signs, whichideallycould allow providers to intervene when health starts to deteriorate, as opposed to after a patient starts reporting symptoms.

Its not a new idea. But Dr. Steve Xu, medical director at Northwestern Universitys Center for Bio-Integrated Electronics, said he envisions a world where patients could one day have implanted sensors that not only monitor vital signs but also provide automated health insightstransforming healthcare into a system where patients are constantly provided feedback on their health status.

He said he could see that proliferating in the next 20 years, and doesnt think an implantable sensor would be an insurmountable privacy concern for patients. Implantable devices are already being used in healthcare, including birth-control implants and nerve stimulators. However, it would be on companies to provide evidence that these sensors are actually helpful for patient health and transparency into how the data is being used.

Xus research at Northwestern involves working on wearable sensors for pediatric care, such as to better monitor newborns who are born prematurely. Already, one-third of consumers report owning a wearable device to help track their health, according to a 2019 report from the Stanford Medicine Center for Digital Health and early-stage digital health venture fund Rock Health. While most of those devices track more general exercise, sleep and heart rate, and arent used for medical care, they could point to patient interest and comfort with monitoring health data.

And health systems have been looking at the space more closely too. To lay the groundwork for better remote monitoring of patients, such as after discharge, UCHealth in Colorado partnered with startup BioIntelliSense to help develop its health-monitoring patch, as well as to support the company as it sought regulatory clearance. About the size of a Band-Aid, the patch continuously tracks metrics like heart rate, skin temperature and respiratory rate and sends the data back to a provider.

BioIntelliSense earned U.S. Food and Drug Administration clearance for the device earlier this year.

Xu said he expects to see a tipping point within the next decade when almost everyone will collect data with wearable devices, sensors or patches, which can be linked with medical records.

He points to how in the 1980s, it was difficult to imagine everyone would have a cellphone. Flip phones in the mid-2000s provided a shift in perspectiveMotorola came out with the Razr flip phone, and that was a turning point, where things were really coolbut it wasnt until the BlackBerry and Apples iPhone that adoption really took off.

While wearables available today have shown promise for fitness tracking and some limited medical functions like conducting electrocardiograms, theres still opportunities for what the future is, Xu said, which developers will continue to build on. I think these wearables are probably at the flip-phone stage, he added.

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Biotech innovations to spur next phase of personalized care - ModernHealthcare.com

Battelle and The Ohio State University Wexner Medical Center have jointly developed a new rapid, sensitive diagnostic test for COVID-19. The Ohio State Wexner Medical Center will administer the new test under its existing FDA certification permits. This will increase and improve test processing in Ohio according to existing state clinical guidelines.

The new rapid test will allow for faster turnaround time on test results, which will help flatten the curve.

Battelle researchers spent several weeks working in the companys West Jefferson labs to develop a diagnostic assay and complete a validation process, with early results suggesting exceptionally high sensitivity.

Since March 14, more than 100 Ohio State Wexner Medical Center researchers and clinicians have worked with Battelle researchers nights and weekends to stand up the lab that will support COVID-19 testing. After enough data was gathered by researchers at both institutions, Ohio State processed its first 91 tests for diagnosis Wednesday using cutting-edge Battelle and Ohio State equipment in a Centers for Medicare & Medicaid Services (CMS)-certified pathology lab at Ohio State.

Battelle is now working to bring a second lab online in West Jefferson, with the intent of making more test processing available. Battelle is in the process of receiving a Clinical Laboratory Improvement Amendment (CLIA) from CMS to begin its own clinical testing.

Ohio State and Battelle teams have shown incredible leadership and ingenuity in moving this project forward so rapidly, said Ohio Gov. Mike DeWine. With this collaboration, we will increase testing right here in Ohio to better help health care professionals and public health officials understand, treat and prevent the spread of the virus.

Results of the test can be available in as few as five hours. Initially, the system can process approximately 200 tests per day, but when the infrastructure is fully built over the coming weeks, the goal is to process more than 1,000 test swabs per day.

Battelle has decades of experience in infectious disease research and has worked with virtually all federal health and national security agencies to respond to emerging health threats, said Lou Von Thaer, Battelles president and CEO. I am incredibly proud of the Battelle team, the speed at which it was able to work around the clock to quickly get this operational, and our collaboration with The Ohio State University.

Battelles infectious disease, genetic and virology experts teamed up with researchers and scientists across Ohio States College of Medicine, including immunologists, microbiologists, pathologists, epidemiologists and data analytics researchers for this project.

Were proud of the partnership of our dedicated scientists with Battelle researchers to help find innovative solutions for the coronavirus pandemic sweeping the world, said Dr. Hal Paz, executive vice president and chancellor for health affairs at Ohio State and CEO of the Ohio State Wexner Medical Center. Our physicians and nurses are eager to start administering these tests that will greatly increase our capacity to diagnose more people and assist us in finding solutions for this disease. Testing is just one of more than 50 new research areas aimed at combatting COVID-19 underway at the Wexner Medical Center. We are working hand in hand with Battelle on many of these critical projects.

Battelle is contributing its expertise and using its specialty facilities, including the largest, private BSL-3 laboratory in the United States, and is actively working on several other solutions related to the COVID-19 pandemic.

COVID-19 testing requires an order from a physician or other advanced practice provider. Based on feedback from the Ohio Department of Health, testing is prioritized for inpatients in hospitals and other facilities, outpatients who are moderately ill but who are at high risk for serious illness (e.g, elderly, immune compromised, underlying lung disease, etc.), health care providers and first responders. Asymptomatic patients do not need to be tested.

People who believe they need to be tested should contact their primary care provider, local hospital or your local health department for further direction.

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Battelle and Wexner Medical Center create new diagnostic test for COVID-19 - The Ohio State University News

Hidden in the virus's unique microscopic fragments are clues to the origins of its original strain. So far, mostcases on the U.S. West Coast are linked to a strainfirst identified in Washington state

SAN FRANCISCO At least eight strains of the coronavirus are making their way around the globe, creating a trail of death and disease that scientistsare tracking by their genetic footprints.

While much is unknown, hidden in the virus's unique microscopic fragments are clues to the origins of its original strain, how it behaves as it mutates and which strains are turning into conflagrations while others are dying out thanksto quarantine measures.

Huddled in once bustling and now almost empty labs, researchers who oversaw dozens of projects are instead focused on one goal:tracking the currentstrains of the SARS-CoV-2 virus that cause the illness COVID-19.

This story is provided free to the community to keep readers informed about coronavirus. | If local news is important to you, please consider a digital subscription.

Labs around the world are turning their sequencing machines, most about the size of a desktop printer, to the task ofrapidly sequencing the genomes of virus samples taken frompeople sick with COVID-19.The information is uploaded to a website called NextStrain.org that shows how the virus is migrating and splitting into similarbut new subtypes.

While researcherscaution they'reonly seeing the tip of the iceberg, the tiny differences between the virus strains suggest shelter-in-place orders are working in some areas and thatno one strain of the virus ismore deadly than another. They also say it does not appear the strains will grow more lethal as theyevolve.

"The virus mutates so slowly that the virus strains are fundamentally very similar to each other," said Charles Chiu, a professor of medicine and infectious disease at the University of California, San Francisco School of Medicine.

The SARS-CoV-2 virusfirst began causing illness in China sometimebetween mid-November and mid-December. Its genome is made up of about 30,000 base pairs. Humans, by comparison, have more than 3 billion. So fareven in the virus's most divergent strainsscientists have found only 11 base pair changes.

That makes iteasy to spot new lineages as they evolve, said Chiu.

"The outbreaks are trackable. We have the ability to do genomic sequencing almost in real-time to see what strains or lineages are circulating," he said.

So far, mostcases on the U.S. West Coast are linked to a strainfirst identified in Washington state. It may have come from a man who had been in Wuhan, China, the virus epicenter, and returned home on Jan. 15. It is only three mutations away from the original Wuhan strain, according to work done early in the outbreakby Trevor Bedford, a computational biologist at Fred Hutch, a medical research center in Seattle.

On the East Coast there are several strains, including the one from Washington and others that appear to have made their way from China to Europe and then to New York and beyond, Chiu said.

Beware pretty phylogenetictrees

This isnt the first time scientists have scrambled to do genetic analysis of a virus in the midst of an epidemic. They did it with Ebola, Zika and West Nile, but nobodyoutside the scientific community paid much attention.

"This is the first time phylogenetic trees have been all over Twitter," said Kristian Andersen, a professor at Scripps Research, a nonprofit biomedical science research facility in La Jolla, California, speaking of the diagrams that show the evolutionary relationships between different strains of an organism.

The maps are available on NextStrain, an online resource for scientists that uses data from academic, independent and government laboratories all over the world to visually track the genomics of the SARS-CoV-2 virus. It currently represents genetic sequences of strains from 36 countries on six continents.

While the maps are fun, they can also be "little dangerous" said Andersen. The trees showing the evolution of the virus are complex and its difficult even for experts to draw conclusions from them.

"Remember, were seeing a very small glimpse into the much larger pandemic. We have half a million described cases right now but maybe 1,000 genomes sequenced. So there are a lot of lineages were missing," hesaid.

Different symptoms, same strains

COVID-19 hitspeople differently, with some feeling only slightly under the weather for a day, others flat on their backs sick for two weeks and about 15% hospitalized. Currently, an estimated1% of those infected die. The rate varies greatly by country and experts say it is likely tied to testing rates rather than actual mortality.

Chiu says it appears unlikely the differences are related to people being infected withdifferent strains of the virus.

"The current virus strains are still fundamentally very similar to each other," he said.

The COVID-19 virus does not mutate very fast. It does so eightto 10 times more slowly than the influenza virus, said Anderson, making its evolution rate similar to other coronaviruses such asSevere Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).

Its also not expected tospontaneously evolve into a form more deadly than it already is to humans. The SARS-CoV-2 is so good at transmitting itself between human hosts,said Andersen,it is under no evolutionary pressure to evolve.

Shelter in place working in California

Chius analysis shows Californias strict shelter in place efforts appear to beworking.

Over half of the 50 SARS-CoV-2 virus genomes his San Francisco-based lab sequenced in the past two weeks are associated with travel from outside the state. Another 30% are associated with health care workers and families of people who have the virus.

"Only 20% are coming from within the community. Its not circulating widely," he said.

Thats fantastic news, he said, indicating the virus has not been able to gain aserious foothold because of social distancing.

It's like a wildfire, Chiu said. A few sparks might fly off the fire and land in the grass and start new fires. But if the main fire is doused and itsembers stomped out, you can kill offan entire strain.In California, Chiu sees a lot of sparks hitting the ground, most coming from Washington,but they're quickly being put out.

An example wasa small cluster of cases in Solano County, northeast of San Francisco. Chius team did a genetic analysis of the virus that infected patients there and found it was most closely related to a strain from China.

At the same time, his lab was sequencing a small cluster of cases in the city of Santa Clara in Silicon Valley. They discovered the patients there had the same strain as those in Solano County. Chiu believes someone in that cluster had contact with a traveler who recently returned from Asia.

"This is probably an example of a spark that began in Santa Clara, may have gone to Solano County but then was halted," he said.

The virus, he said, can be stopped.

China is an unknown

So far researchers dont have a lot of information about the genomics of the virus inside China beyond the fact that it first appeared in the city of Wuhan sometime between mid-November and mid-December.

The viruss initial sequence was published on Jan. 10 by professor Yong-Zhen Zhang at the Shanghai Public Health Clinical Center. But Chiu says scientists dont know if there was justone strain circulating in China or more.

"It may be that they havent sequenced many cases or it may be for political reasons they havent been made available," said Chiu. "Its difficult to interpret the data because were missing all these early strains."

Researchers in the United Kingdom who sequenced the genomes of viruses found in travelers from Guangdong in south China found those patients strains spanned the gamut of strains circulating worldwide.

"That could mean several of the strains were seeing outside of China first evolved there from the original strain, or that there are multiple lines of infection. Its very hard to know," said Chiu.

The virus did not come from a lab

While there remain many questions about the trajectory of the COVID-19 disease outbreak, one thing is broadly accepted in the scientific community: Thevirus was not created in a lab but naturally evolved in an animal host.

SARS-CoV-2s genomic molecular structure thinkthe backbone of the virus is closest to a coronavirus found in bats. Parts of its structure also resemble a virus found in scaly anteaters, according to a paper published earlier this month in the journal Nature Medicine.

Someone manufacturing a virus targetingpeople would have started with one that attacked humans, wrote National Institutes of Health Director Francis Collinsin an editorial that accompanied the paper.

Andersen was lead author on the paper. He said it could have been a one-time occurrence.

"Its possible it was a single event, from a single animal to a single human," and spread from there.

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8 strains of coronavirus are circling the globe; heres the clues theyre giving scientists - Canton Repository

Covid-19 proliferates freely across the region. The more people with whom you come in contact, the greater likelihood you will contract it. Your age, health and genetics will dictate whether you get sick, end up hospitalized or die.

You also may need to reconsider your Easter plans.

These are the conclusions at this point from Dr. Thomas A. Russo, chief of the Division of Infectious Diseases in the University at Buffalo Jacobs School of Medicine and Biomedical Sciences.

The number of people impacted regionally will grow in the weeks to come, he said.

"Of those who are symptomatic based on data to date, about 80%, maybe 85%, have less serious disease that does not require hospitalization; about 15% require hospital treatment; and about 5% become critically ill, said Russo, who also works at the VA Medical Center in Buffalo, where at least four patients were on ventilators with Covid-19 late last week.

He talked with The Buffalo News about the dangers of the novel coronavirus and the mysteries that cloud saving the sickest of its victims. Below are excerpts.

Dr. Thomas Russo, professor and chief of infectious diseases in the University at Buffalo Jacobs School of Medicine and Biomedical Sciences. (Photo courtesy of UB)

Q: What are the symptoms?

Someone could be minimally symptomatic, which could be some combination of fever, rhinitis (stuffiness and runny nose), sore throat. They could have a mild cough, more of an upper respiratory tract infection. Loss of taste or smell were first anecdotally recognized in England and are being increasingly described. I certainly think those are symptoms that someone could develop early on as well.

Q: Are these symptoms emblematic of other conditions, too?

Flu and other respiratory viruses can mimic them. Right now, we still have circulating Influenza A, Influenza B, and some parainfluenzas (respiratory viruses that differ from the flu) around. In the absence of a diagnostic test, it's very difficult to be absolutely sure. Flu is on the downswing right now. Because coronavirus is starting to become the dominant virus in Western New York, its more likely to be coronavirus.

Seven ways to build Covid-19 resilience and ease your anxieties

Q: Do epidemiologists have a sense about how often people are asymptomatic?

That is part of the problem. Right now, the kits we use to test the RNA of the virus, the genetic footprint, arent being used on people that are asymptomatic. We're saving our tests for the most part for people with symptoms that are critically ill, so the tests are not a good tool to gauge what proportion of the population is asymptomatic.

People can be asymptomatic and be infected and able to spread the virus.

Q: Why does the disease progress in some people and not others?

The biology depends on our genetics and probably how much of the virus we get. If someone gets a huge dose of the virus, it may be such that the hosts defenses which are imperfect because we've never seen this virus before may be overwhelmed. If you get a lower dose, combined with the genetics, you may hopefully have a milder course. Everyone can be a little different.

Greater exposure to the coronavirus almost certainly raises your risk of infection and may boost the chance you will get sicker.

Q: How do you get a small dose versus a big dose?

The people who are going to be at risk for a large dose are those in close contact with someone whos infected with coughing and sneezing for prolonged periods of time. They're constantly going to be shedding virus. If you're in contact with multiple individuals, you may get sort of multiple repeat doses over time. Whether that's better or worse than with one person who is sick, who knows?

Q: What symptoms tend to first appear?

I'm not aware of any pecking order. I can tell you through years of experience in infectious diseases that were all different in terms of how we present which symptoms, what combination of symptoms, how severe. We're obviously seeing that with the new coronavirus as well.

Q: When is it time to get medical help?

Present recommendations are that if you develop an upper respiratory tract infection, even with a fever or cough, you're going to feel a little bit miserable but not critically ill. It's OK to touch base with your primary care physician. You should sort of isolate yourself at that point. The critical tell is always shortness of breath, which suggests you're developing pneumonia. That's the complication that we're concerned about. If pneumonia becomes extensive, you have problems with oxygen exchange and as that difficulty increases, that's when you end up on a ventilator.

Q: Is there anything to beat this back once you start to notice that your taste or sense of smellhas left you and that you're starting to develop other symptoms?

Using Star Trek terminology, our shields are completely down. With the flu, even if we've had a bad match in the vaccine, we've still got 30-40% of our shields. We've also got Tamiflu, which we know can both prevent disease and shorten symptoms. But so far for this new coronavirus, we have no drugs. We have no vaccine. We're all susceptible.

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Q: Who is most at risk in Western New York?

The vulnerable population with underlying cardiac disease, underlying pulmonary disease, underlying immunocompromised states due to certain cancers or drugs they may be on. Diabetes and hypertension have also been associated. It certainly makes sense that if you're a smoker, you're going to be an increased risk.

We think probably people that are older are still at increased risk, even if they don't have any comorbidities, but it seems the comorbidities are a little bit more important. I'd probably rather be a 70-year-old with no comorbidities than a 60-year-old with bad lungs and heart. The relative risk we're still sorting out. And even though younger adults and children are in terms of a bad consequences relatively spared, with significantly less risk, they're not absolutely bulletproof.

Q: Who should limit contact with others right now and what should be the threshold?

The smaller the number, the better. As the number increases, you're increasing your likelihood of getting infected, and that likelihood increases as the prevalence of infection in our community increases, which is happening right now. It's a mathematical thing. If the prevalence is increased tenfold, then it takes tenfold less people to potentially be exposed. We need to button down with our social distancing more than ever to cut the prevalence.

Q: What about big celebrations like Easter?

A common question Im getting is, I want to have a small group gathering for Easter, can I do it safely? The answer is no, you cant do so with 100% certainty. Theres the whole asymptomatic issue, which makes it impossible to be sure that you are not infected.

Both parties need to be quarantined for 14 days, not previously infected. It has to be rigorous. It can't be you running out to work, running out to Wegmans. You really can't have that contact with anyone. And as long asyou follow that and both parties are fine at the end of 14 days, then when you get together you want to really practice modified social distancing. No kissing, hugging, sharing any sort of foods and utensils, anything where there could be sort of transference of saliva or respiratory secretions. Maintain rigorous hand hygiene, especially after contacting high-touch areas such as phones, refrigerator door handles, TV remotes, etc. You're gonna minimize risk, but you can't drive it to zero.

How to celebrate Easter, Passover and Ramadan in the midst of coronavirus

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UB infectious disease doctor breaks down Covid-19 and its potential impact on WNY - Buffalo News

MAVERICK-HCM Phase 2 Clinical Trial Results Consistent with Tolerability Observations from Prior Studies of Mavacamten

Improvement in NT-proBNP and Troponin Levels Support Future Development in Non-Obstructive HCM and Heart Failure with Preserved Ejection Fraction (HFpEF)

MyoKardia to Host Webcast Conference Call at 4:30 p.m. EDT

BRISBANE, Calif., March 30, 2020 (GLOBE NEWSWIRE) -- MyoKardia, Inc. (MYOK) today announced results from the dose-ranging MAVERICK-HCM Phase 2 clinical trial of mavacamten for the treatment of non-obstructive hypertrophic cardiomyopathy (HCM). Data were presented during a late-breaker session at the American College of Cardiologys 69th Annual Scientific Session together with the World Congress of Cardiology (ACC.20/WCC Virtual) In the MAVERICK-HCM study, mavacamten was generally well tolerated, and statistically significant improvements in key biomarkers of cardiac injury and wall stress were observed. Further, subgroup analyses of study participants with indicators of more advanced disease demonstrated clinical responses across multiple parameters among patients on active treatment versus placebo.

Non-obstructive HCM is especially challenging to treat as there are no proven or approved pharmacological therapies. Thus, for patients who develop symptoms refractory to medications, cardiac transplantation may be the only option, saidCarolynHo, M.D., Medical Director of the Cardiovascular Genetics Center at Brigham and Womens Hospital and lead author on behalf of the MAVERICK-HCM study investigators. Although the primary objective of MAVERICK was to assess the safety and tolerability of mavacamten in non-obstructive HCM, in exploratory analyses we observed an encouraging result with reductions in serum levels of NT-proBNP, a biomarker of hemodynamic stress, and also cardiac troponin I, a biomarker of myocardial injury. We believe MAVERICK is the first study to show an improvement in important serum biomarkers in this patient population and suggests that there is potential physiological benefit from the drug. We were also intrigued by findings that patients with more severe disease expression, those with elevated serum troponin levels or evidence of diastolic dysfunction by echo, may have achieved functional benefit. These findings, combined with mavacamtens tolerability profile, are encouraging, and they provide direction for further evaluation of mavacamten for patients with non-obstructive HCM.

MAVERICK has succeeded in providing us with the important data we needed to proceed in our planned clinical trials in non-obstructive HCM, as well as a targeted subset of patients with heart failure with preserved ejection fraction, or HFpEF. We gained unique insights into dosing strategies using markers linked to clinical benefit, as well as how to identify patients who may be most likely to benefit from mavacamten, said Jay Edelberg, M.D. Ph.D., MyoKardias Senior Vice President of Development. The MAVERICK results also further our confidence in mavacamtens development in obstructive HCM, as we approach our Phase 3 EXPLORER-HCM readout, which is expected in the second quarter.

MAVERICK-HCM ResultsSafety and Tolerability ObservationsMavacamten was generally well tolerated, consistent with prior clinical studies.

Effect on Exploratory Endpoints of Efficacy: Biomarkers of Cardiac Wall Stress and Injury Among several pre-specified endpoints analyzed, treatment with mavacamten resulted in significant changes in circulating biomarkers associated with heightened risks of cardiac complications.

For the intent-to-treat population, no difference was observed between active and placebo groups in the other exploratory endpoints.

The effect of mavacamten on NT-proBNP and cardiac troponin levels in non-obstructive HCM patients is a first-of-its-kind finding for a product candidate in this patient population, said Michael R.Zile, M.D.,Director of Cardiology, Ralph H. Johnson VA Medical Center. NT-proBNP is a measure of cardiac wall stress, and elevated troponins signal heart muscle injury, both of which have been established in the literature as prognosticators of dire complications in both HCM and HFpEF patients, including the need for hospitalizations, surgical intervention and death. The reductions in biomarkers associated with poor outcomes are encouraging, and I look forward to seeing the potential for mavacamten to impact outcomes in HCM, as well as certain targeted HFpEF populations, over time.

Story continues

Patient Subgroups with Advanced Diastolic Disease MyoKardia also shared its analyses of the effect of mavacamten treatment on two subgroups of patients with advanced disease: one comprising 19 of the 59 enrolled patients (32%) with elevated cardiac troponin levels of >0.03ng/mL and another including 25 patients (42%) who had elevated filling pressures, defined by E/e >14(4). HCM patients with higher cardiac troponin levels are known to be at greater risk for serious complications, and elevated filling pressures are indicative of impaired diastolic compliance, or the ability of the left ventricle to relax and fill with oxygenated blood.

A trend toward potential benefit was observed across numerous clinical measurements in patients with elevated cardiac troponin I levels and those with higher diastolic filling pressures versus placebo:

Composite Functional Endpoint Analysis A composite functional endpoint(4) analysis was utilized to compare responses among the intent-to-treat population and the subgroups of patients with more advanced disease to those within the placebo population.

Based on our observations that multiple markers responded to mavacamten, we believe we may be able to utilize markers of likely clinical benefit to guide dosing in the non-obstructive HCM patient population moving forward, similar to the way we are utilizing LVOT gradient to guide dosing in obstructive HCM, said Jay Edelberg, M.D., Senior Vice President, Development at MyoKardia. Additionally, we observed in MAVERICK that patients who were most impaired showed the most meaningful trends toward benefit with mavacamten treatment within the 16-week treatment period. We look forward to leveraging these learnings, as well as knowledge gained from the longer exposures to treatment provided by our long-term extension study, as we look to advance mavacamten for the treatment of non-obstructive HCM patients and adjacent HFpEF populations.

Data from the MAVERICK-HCM Phase 2 clinical trial were presented by Carolyn Ho, M.D., Medical Director of the Cardiovascular Genetics Center at Brigham and Women's Hospital and Associate Professor of Medicine at Harvard Medical School, during the American College of Cardiologys Annual Scientific Session together with World Congress of Cardiology virtual meeting this morning during the Featured Clinical Research III Session in a presentation titled Mavacamten Improves Biomarkers Of Myocardial Wall Stress And Injury In Patients With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy (nHCM): Results From The Phase 2 MAVERICK-HCM Study (#412-16).

About the Phase 2 MAVERICK-HCMClinical TrialThe Phase 2 MAVERICK-HCM trial assessed the safety and tolerability of a range of exposures over 16 weeks of treatment in patients with symptomatic, non-obstructive HCM. All study participants were required to be diagnosed with non-obstructive HCM, with left ventricular wall thickness either 15mm or 13mm with a family history of HCM,New York Heart Association(NYHA) classifications of Class II or III, and NT-proBNP levels of greater than 300 pg/mL at rest.Baseline characteristics, such as age, weight, gender, pathogenic mutation status, background beta blocker use, NYHA classification and exercise capacity were evenly distributed between active and placebo arms.

A total of 59 participants were enrolled in the study and randomized into one of three groups to receive once-daily doses of mavacamten or placebo.The active mavacamten treatment arms were designed to assess a range of drug concentrations around target levels of 200 ng/mL and 500 ng/mL. All participants in the active treatment arms began the study receiving 5mg doses of mavacamten. At Week 4, pharmacokinetic (PK) assessments were conducted and doses were adjusted in a blinded fashion per the protocol based on the participants assigned cohort. Following the 16-week treatment period, participants were monitored for an additional 8 weeks and became eligible to participate in MyoKardias MAVA Long-Term Extension (LTE) study.

Conference Call and WebcastMyoKardia management will also host a virtual event for investors and analyst today to review the data from MAVERICK-HCM and discuss future development plans for mavacamten in targeted groups of patients with diastolic disease. This live webcast event will begin at 4:30 p.m. EDT / 1:30 p.m. PDT and include remarks by Dr. Anjali Owens, Medical Director, Center for Inherited Cardiac Disease at the University of Pennsylvania, and Dr. Michael Zile, Professor of Medicine at the Medical University of South Carolina.

To access the call, please dial (844) 494-0193 (U.S.) or (508) 637-5584 (international), and reference the conference ID 2982709. A live webcast of the event will be available on the Investors section of MyoKardias website at http://investors.myokardia.com. A replay of the webcast, and accompanying slides, will be available on theMyoKardiawebsite for 90 days following the call.

About Non-obstructive HCM and Heart Failure with preserved Ejection FractionHypertrophic cardiomyopathy is the most common genetic form of heart disease, affecting an estimated one in every 500 people worldwide.There are two main forms of HCM, obstructive HCM and non-obstructive HCM, which often share the same underlying genetic defects in the sarcomere that result in hypercontractility.In non-obstructive HCM, the heart contracts excessively and the left ventricle becomes abnormally thick, restricting the ability of the heart to relax and fill or pump to meet the bodys needs, but no physical obstruction is present in the outflow tract of the left ventricle. Non-obstructive HCM affects an estimated one-third of all HCM patients and presents unique treatment challenges.Patients may progress to a more advanced state of disease than those with obstructive disease before being diagnosed, and there are no approved pharmacological treatment options available.As non-obstructive HCM progresses, symptoms begin to resemble those of a congestive heart failure patient and heart transplantation may become the only viable treatment option.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome, which in many patients is characterized by impairment of the left ventricles ability to relax and fill during diastole, resulting in insufficient blood flow to meet the bodys needs.HFpEF is estimated to affect approximately three million people in the U.S. and is associated with significant morbidity and mortality. There are currently no approved therapies for HFpEF.

About Mavacamten (MYK-461)Mavacamten is a novel, oral, allosteric inhibitor of cardiac myosin being developed for the treatment of hypertrophic cardiomyopathy (HCM). Mavacamten is intended to reduce cardiac muscle contractility by inhibiting the excessive myosin-actin cross-bridge formation that underlies the excessive contractility, left ventricular hypertrophy and reduced compliance characteristic of HCM.MyoKardiais currently evaluating mavacamten in multiple clinical trials for the treatment of obstructive and non-obstructive HCM. The pivotal Phase 3 clinical trial, known as EXPLORER-HCM, is being conducted in patients with symptomatic, obstructive HCM andMyoKardiaanticipates data from this program in the second quarter of 2020. Two long-term follow-up studies are also ongoing, the PIONEER open-label extension study of obstructive HCM patients from MyoKardias Phase 2 PIONEER trial and the MAVA-LTE, an extension study for patients who have completed either EXPLORER-HCM or MAVERICK-HCM, the companys Phase 2 clinical trial of symptomatic non-obstructive HCM patients. InApril 2016, the U.S.FDAgranted Orphan Drug Designation for mavacamten for the treatment of symptomatic obstructive HCM.

About MyoKardiaMyoKardia is a clinical-stage biopharmaceutical company discovering and developing targeted therapies for the treatment of serious cardiovascular diseases. The company is pioneering a precision medicine approach to its discovery and development efforts by 1) understanding the biomechanical underpinnings of disease; 2) targeting the proteins that modulate a given condition; 3) identifying patient populations with shared disease characteristics; and 4) applying learnings from research and clinical studies to inform and guide pipeline growth and product advancement. MyoKardias initial focus is on small molecule therapeutics aimed at the proteins of the heart that modulate cardiac muscle contraction to address diseases driven by excessive contraction, impaired relaxation, or insufficient contraction. Among its discoveries are three clinical-stage therapeutics: mavacamten (formerly MYK-461); danicamtiv (formerly MYK-491) and MYK-224.

MyoKardias mission is to change the world for people with serious cardiovascular disease through bold and innovative science.

Forward-Looking StatementsStatements we make in this press release may include statements which are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are usually identified by the use of words such as "anticipates," "believes," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "will," and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Securities Exchange Act and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements, including statements regarding the clinical and therapeutic potential of mavacamten, our plans to advance the clinical development of mavacamten in non-obstructive HCM patients and a targeted population of HFpEF patients, the anticipated data readout from our Phase 3 EXPLORER trial of mavacamten, our plans to consult with the FDA on potential pathways to registration and to provide a regulatory update, the initiation, progress and availability of data from our ongoing and planned clinical trials, and the timing of these events, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, risks associated with the development and regulation of our product candidates, as well as those set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, and our other filings with the SEC. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts Michelle Corral Executive Director, Corporate Communications and Investor Relations MyoKardia, Inc. 650-351-4690 ir@myokardia.com

Hannah Deresiewicz (investors) Stern Investor Relations, Inc. 212-362-1200 hannah.deresiewicz@sternir.com

Julie Normant (media)W2O628-213-3754jnormart@w2ogroup.com

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MyoKardia Announces Mavacamten Treatment Well Tolerated and Significantly Reduced Biomarkers of Cardiac Injury and Wall Stress in Non-Obstructive...

When Amber Freed (MACC 04) graduated from Daniels College of Business at DU, she knew her education had prepared her for an exciting career in finance. What she didnt expect was how well it would prepare her for her lifes work: fighting for her sons life.

In 2018, Amber and her husband, Mark, had noticed that their son, Maxwell, was not achieving the same milestones as his twin sister, Riley. He didnt reach for toys or use his hands to grasp. After extensive genetic testing, the Denver couple received news of their 16-month-old sons diagnosis: SLC6A1. So rare that it doesnt have a name and is referred to by the affected gene, the disease causes developmental delay and the onset of debilitating epilepsy by age 3 or 4, as Amber describes. Time was of the essence Maxwell needed treatment before that stage to prevent irreversible neurological damage.

The problem was that no treatment for SLC6A1 yet existed. Amber decided to help create it.

Amber was working as an equity analyst at Janus Henderson Investors at the time of her sons diagnosis, and she quit her job the day she heard the news. She would dedicate her energy full time to finding the solution gene replacement therapy for Maxwell and other children with SLC6A1. Since that time, she says she has devoted 80 hours per week to networking with scientists, physicians, and pharmaceutical companies, in addition to caring for her twin children and providing multiple therapies for Maxwell.

Solving big social issues, Amber says, is a skill she learned during her time at the University of Denver. A member of the Pioneer Leadership Program, she was drawn to DU because of its high values and mission, as well as the way the University pulls students together. She came from a life of poverty in Pueblo about two hours south of Denver with little parental support. She knew education was the key to making a better life for herself.

At DU, Amber found a community of people who would take her under their wing and help her manage lifes challenges and solve problems along her educational journey. She emerged from DU with an understanding that the way to change the world is by solving a huge societal issue. She says finding a cure for Maxwell and others affected by the same genetic disease is the most consequential challenge of her life.

Throughout my education at DU, in addition to my major, DU supplied me with the tools to teach me how to think and how to solve a problem by bringing key stakeholders together, while using the highest moral integrity to do so, Amber says. Even though accounting was my major, with Maxwells diagnosis I was forced to become an expert in microbiology overnight. The holistic DU experience is what separates DU from everyone else. This isnt a path that I would have expected, but DU prepared me to do it.

Working with Dr. Steven Gray at the University of Texas Southwestern Medical Center in Dallas, Amber says she is about to set the record for fastest time from newly discovered disease to curative treatment. She is in the process of raising $4 million to fund the research and clinical trials for SLC6A1.

This treatment is Maxwells only chance at life, and in her advocacy, Amber feels she is speaking for all the children with SLC6A1 who dont have a voice. The treatment itself, she says, is once and done: a two-hour process that uses a harmless virus to replace the faulty DNA in the childs body. It sounds like science fiction, Amber says, but its possible today.

The impact for the disease itself will have an effect far beyond her family, Amber says. She and Dr. Gray envision SLC6A1 being a part of a newborn screening panel: babies will be screened and treated before they leave the hospital. Since its a single treatment that changes the DNA and solves the issue, those babies will never get sick from the disease. Additionally, the treatment approaches of other diseases affected by the same gene would benefit greatly from Dr. Grays work.

My dream is for there to never be another child with SLC6A1, Amber says. I dont want any other family to go through what we are going through.

To the DU community, Amber has one message: Thank you.

This is every parents worst nightmare, and the only way to solve it is through collective effort of knowledge, resources, and kindness. Ive been blown away by DU. Im so proud to be an alum, she says.

In 2012, Amber was highlighted in the book Shortcut to Prosperity as an example of grit. She says a great deal of her grit came from her DU experience. Because of her DU education, Amber says, something nearly miraculous is coming from a person who really didnt have a chance at life.

Her DU network continues to join her in the journey. Ambers first call for volunteers was on a Pioneer Leadership Program Facebook group. Undergraduate student Brandon Prentice was the first to step forward, offering to use his biology background to help in any way he could. Now he has a role within Ambers organization and is the primary author on a research paper a tremendous accomplishment for an undergraduate student. Brandon is about to start medical school at Oakland University William Beaumont, and he has a new vision for his career: curing rare diseases.

As the director of research for SLC6A1 Connect, I partnered with Amber as she began developing a cure for SLC6A1-related disorders, says Prentice. Though Amber was already well positioned to undertake such a daunting task, I served as her scientific tour guide as she entered the complex world of medicine. I provided briefings on research articles, defined laboratory tools like recombinant DNA, and acted as a sounding board as she chose what to do next. I am beyond grateful that I had the opportunity to further develop these skills and am even more grateful for the time observing Ambers strengths. She has advocated for those who are suffering, she has displayed compassion, she has overcome setbacks, and she has provided direction for the medical community. Amber is impressive, and I hope to emulate that same vigor as a future physician.

Ambers fellow accounting major Nat Borchers of Colorado Rapids and Portland Timbers soccer fame reached out to his network and obtained signed sports memorabilia for Ambers silent auction. DUs head basketball coach, Rodney Billups, is participating in Ambers upcoming fundraising golf tournament. Those are just a few of her DU connections helping her to solve the problem of a lifetime.

Ambers mission her tireless work to solve SLC6A1 for Maxwell and other children is one of hope and progress. Her DU education and her DU network are joining her every step of the way.

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Solving the Challenge of a Lifetime - University of Denver