Drug Discovery Archives - Sanford Burnham Prebys
Institute News

A year-end note from David Brenner

AuthorDavid Brenner
Date

December 19, 2023

This past year — my first full calendar year as president and CEO of Sanford Burnham Prebys — has been exciting and immensely rewarding. We’ve accomplished a lot and, more importantly, laid the groundwork for a wealth of future achievements.

It begins with having a plan. We are in the midst of a biomedical revolution, one in which the old ways of thinking about and doing science no longer address the complexities of modern research or the greater needs in public health.

Sanford Burnham Prebys is particularly positioned to adapt and lead in this new world by combining distinct and powerful resources with a unified mission driven by ambitious goals that emphasize disease-focused centers combined with enabling technology programs.

Of course, doing so requires a brilliant faculty, one that boasts exceptional skills and vision not just in this moment, but in the years to come. Our faculty know what to do. Our newest faculty promise to further propel and elevate. In less than a year, we have hired eight early-career scientists and physicians, an unprecedented number in such a short time.

They are among the best and brightest, coming from elite labs and institutions across the country: Shengie Feng, PhD (Howard Hughes Medical Institute and UCSF); Kelly Kersten, PhD (UCSF); Angela Liou, MD (Children’s Hospital of Philadelphia) Sanjeev Ranade, PhD (Gladstone Institutes); Sanju Sinha, PhD (National Cancer Institute); Xueqin Sherine Sun, PhD (Cold Spring Harbor Laboratory); Kevin Tharp, PhD (UCSF); and Xiao Tian, PhD (Harvard Medical School).

A couple have already started their next chapters of their careers at Sanford Burnham Prebys, including already landing new grants! Others begin in January or March. Please welcome them.

These eight scientists represent the first wave. There are more to come, the benefit of Denny Sanford’s landmark gift early in 2023.

It has been a robust year in science at Sanford Burnham Prebys, too.

The Cancer Center received a merit extension from the NCI related to its support grant, a rare recognition of ongoing excellence. The Prebys Center for Chemical Genomics continues to be the go-to place for drug discovery, highlighted by a trio of recent awards totaling almost $25 million to pursue novel leads and promising therapies to treat all manners of addiction.

Sanford Burnham Prebys researchers are pushing boundaries across disciplines, from DNA loops in pediatric brain tumors and a sugar with anti-cancer properties to a heart attack study that could change regenerative medicine and discovering that an incurable liver disease might just be curable.

We’ve also welcomed two new trustees: Michael R. Cunningham, PhD and Lori Moore.

It’s been a busy year. It’s been a good year.

With all of you, next year will be even better.

Institute News

Sanford Burnham Prebys hosts top life-science VC firm to learn the secrets of getting funded

AuthorMonica May
Date

February 26, 2019

There’s no way around it: Developing medicine is costly. The average drug takes about $2.6 billion to develop through FDA approval, according to the Tufts Center for the Study of Drug Development. With a price tag that high, securing venture capital (VC) funding is critical for turning a scientist’s discovery into reality.

This month, Kirsten Leute of Osage University Partners (OUP), a top life-science VC firm, spoke to SBP scientists about best practices and common pitfalls when making a VC pitch. 

Anjali Gupta, a graduate student in the laboratory of Karen Ocorr, PhD, assistant professor at SBP, attended the presentation and explained why the insights are so valuable. 

“Drug discovery is a complex and expensive process. It’s important to understand how bench science can be translated into successful products—in this case, potentially life-saving medicines,” says Gupta. “At SBP, scientists are investigating the underlying causes of rare, debilitating diseases and looking for cures for cancer, heart failure, Alzheimer’s disease and more by discovering novel therapeutic targets, signaling pathways, and mechanisms. By knowing the funding options and strategies available, we can make more informed decisions about our discoveries and increase the probability of developing our research into medicines for patients who need these treatments.” 

Below are seven tips Leute shared to help scientists navigate building a start-up and getting it funded. 

  1. It’s all about the team. VC firms look for an investable management team. Is this the leadership team’s first start-up? Or are they serial entrepreneurs? What skills do they have, and which do they lack? Being a novice entrepreneur isn’t a funding deal breaker—but you may want to consider supplementing your team with experienced partners. 
  2. Pick your partners wisely. The most important relationship decision you make in your life is choosing your significant other. The second most important? Finding your business partners. Many founders bring in colleagues who work down the hall—or even neighbors. But it’s most important to know how you work with one another. Can you argue respectfully? Do you trust that you all have the company’s best interest in mind? 
  3. Do your homework. Before you approach a VC firm, make sure you know its investment focus. Does it specialize in pre-clinical or late-stage assets? Does it lead investments or follow on? In recent years, we’ve seen more crossover investing: firms that invest in a company prior to an initial public offering (IPO). A firm’s focus may shift over time, so make sure to stay up to speed. 
  4. Contact the right person. At most firms, each individual has a specialty, such as immunotherapy. So, if you have an immunotherapy product, make sure you’re contacting the individual who works in that area—and not the person who focuses on robotics, for example. 
  5. Mind your budget. VC firms see a lot of pitches. They can spot it if you haven’t budgeted enough—or are budgeting too much—for an activity. If you’re a first-time entrepreneur, it’s best to hire a consultant or find a mentor who can help (see the resources below).
  6. Ask for advice. VC firms love giving advice, which can help strengthen your ultimate pitch for funding. This will also stimulate their interest in your company. Your institute’s technology transfer office may also have helpful resources and connections. 
  7. Show all your cards—even the negative ones. VC firms hate surprises. Make sure you address any concerns or risks up front. The truth always comes out eventually. 

Ready to get your discovery funded? Below are additional resources and reading materials. 

Resources: 

Reading: 

  • Life Sci VC: blog about all things biotech venture capital by scientist turned early-stage venture capitalist Bruce Booth 
  • The Long Run: veteran biotech reporter Luke Timmerman conducts in-depth interviews with biotech newsmakers 
  • Nature’s bioentrepreneur: practical advance and guidance for starting a biotech company 

 

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries. 

Institute News

Nanowire arrays allow electrical recording of neuronal networks

AuthorJessica Moore
Date

April 12, 2017

To examine a neuron’s health, activity and response to drugs, scientists record its electrical activity. Current methods of recording are destructive, so they can only be used to study a neuron for a brief period, and can only measure the activity of one cell at a time. But neurons don’t function individually—they act in networks, and commonly used systems for detecting the electrical activity of complex groups of neurons aren’t as sensitive as they could be.

A new technology developed through a collaboration between Anne Bang, PhD, director of Cell Biology in the Conrad Prebys Center for Chemical Genomics at the Sanford Burnham Medical Research Institute, and Shadi Dayeh, PhD, associate professor at UC San Diego, makes high-sensitivity recording possible in neuronal networks. Publishing in Nano Letters, the team describes nanowire arrays that could accelerate drug development for neurological and neuropsychiatric diseases.

“We envision that this nanowire technology could be used on stem-cell-derived brain models to identify the most effective drugs for disorders like bipolar disorder and Alzheimer’s,” says Bang.

The nanowire technology developed in Dayeh’s laboratory is nondestructive and can simultaneously measure potential changes in multiple neurons — with the high sensitivity and resolution achieved by the current state of the art.

The device consists of an array of silicon nanowires densely packed on a small chip patterned with nickel electrode leads that are coated with silica. The nanowires poke inside cells without damaging them and are sensitive enough to measure small potential changes that are a fraction of or a few millivolts in magnitude. Neurons interfaced with the nanowire array survived and continued functioning for at least six weeks.

Another innovative feature of this technology is it can isolate the electrical signal measured by each individual nanowire. “This is different from existing nanowire technologies, where several wires are electrically shorted together and you cannot differentiate the signal from every single wire,” Dayeh says.

Dayeh noted that the technology needs further optimization for brain-on-chip drug screening. His team is working to adapt the arrays for heart-on-chip drug screening for cardiac diseases and in vivo brain mapping, which is still several years away. “Our ultimate goal is to translate this technology to a device that can be implanted in the brain.”

This story is based on a press release from UC San Diego.

Institute News

High-throughput screening against a new target for Alzheimer’s drugs

AuthorJessica Moore
Date

March 27, 2017

More than 5 million people in the U.S. have Alzheimer’s, and by 2050 that number could rise as high as 16 million. There are currently no treatments that slow the advance of this cruel disease that slowly destroys a person’s memory and reason. Given the overwhelming need for drugs that prevent or limit the brain degeneration caused by Alzheimer’s, scientists are attacking the problem from all angles.

A new strategy for finding possible Alzheimer’s therapeutics has recently been developed by Nicholas Cosford, PhD, professor at Sanford Burnham Prebys Medical Discovery Institute (SBP), in collaboration with Varghese John, PhD, associate professor at UCLA. The high-throughput screening method, reported in Frontiers in Pharmacology, identified several compounds worthy of further investigation.

“We looked for inhibitors of a process that isn’t the standard target in drug screening for Alzheimer’s,” says Cosford. “This process—generation of a toxic peptide called APP (amyloid precursor protein) delta C31, or the 31 amino acids at the end of APP—may be especially important at early stages of Alzheimer’s, before neurons start to die.”

APP delta C31, which kills neurons, is made when APP is first cut by an enzyme called gamma secretase to form amyloid beta (the best-studied contributor to brain deterioration in Alzheimer’s) and the remaining portion of APP is then further cut by an intracellular caspase enzyme. Amyloid beta—also toxic—sticks together in clumps that clog up the spaces between brain cells. Most of the drugs that have recently been tested in Alzheimer’s patients are intended to eliminate amyloid beta or prevent it from being created, but so far none have been successful in clinical studies.

Cosford and John’s team found several compounds that inhibit production of APP delta C31. “A few of these compounds block signaling pathways not previously implicated in Alzheimer’s—so this is really a new avenue of research that we are pursuing,” adds Cosford.

Worryingly, generation of APP delta C31 is enhanced by statins, drugs that are widely used to lower blood cholesterol. In fact, statins were used in this study to bump up production of APP delta C31 and make reductions in levels of the peptide easier to detect. However, statins also protect against other damaging processes in Alzheimer’s.

“We speculate that whether statins are good or bad in the context of Alzheimer’s may depend on the stage of the disease,” notes Cosford.

“The next step for us is to test the most promising compounds in animal models of Alzheimer’s,” Cosford adds. “We also plan to use the same approach to screen another library of molecules to identify more potential drugs.”

Institute News

The Epstein Family Foundation gives $1M for pancreatic and prostate cancer research

AuthorKristen Cusato
Date

August 10, 2016

Sanford Burnham Prebys Medical Discovery Institute (SBP) has received a $1M donation from The Epstein Family Foundation for scientists to study pancreatic and prostate cancer. The gift, contributed by SBP board member Dan Epstein and his wife Phyllis, will support the lab of Nicholas Cosford, PhD, associate director of Translational Research at the Institute’s NCI-designated Cancer Center.

“Nick Cosford is one of our leading scientists investigating new approaches to treat patients with pancreatic and prostate cancers,” said Perry Nisen, MD, PhD, chief executive officer of SBP. “This generous donation from The Epstein Family Foundation will help us realize our vision to translate fundamental research into clinically meaningful benefit for patients.”

Pancreatic cancer is one of the deadliest forms of cancer. There are no effective therapies and the five-year survival rate is only six percent. Prostate cancer is the second leading cause of cancer death in U.S. men. 180,000 men are diagnosed with prostate cancer every year in this country.

“I am pleased to be able to help advance research, especially in these two challenging types of cancer,” said Epstein, a long-time supporter of SBP who has been a member of the Institute’s board of trustees since 2011. “Nick Cosford is doing some exciting work in his lab and I look forward to hearing about discoveries that may improve the lives of patients diagnosed with these diseases.”

Cosford, who has spent more than 25 years assembling small molecules into disease-fighting chemical compounds, talked about his lab’s focus.

“Aggressive tumor cells, such as those found in pancreatic and advanced prostate cancer, are highly resistant to the normal mechanisms the body uses to eliminate abnormal cells. We are developing medicines that overcome this resistance by inhibiting the pathways tumor cells use to survive. By designing small molecules that act on apoptosis (programmed cell death) and autophagy (a cell survival mechanism), we hope to develop drugs that will destroy deadly tumor cells and improve patient outcomes,” Cosford said.

Institute News

Sanford-Burnham wins GlaxoSmithKline drug discovery challenge

Authorpbartosch
Date

December 1, 2014

We’re excited to announce that a joint team of scientists from Sanford-Burnham at Lake Nona and Mayo Clinic has been selected as a winner of GlaxoSmithKline (GSK)’s 2014 Discovery Fast Track Challenge. The Challenge is designed to accelerate the translation of academic research into novel therapies. Researchers from the two organizations will work with partners at GSK to screen the pharmaceutical company’s library of compounds for potential new drugs to treat resistant hypertension, blood pressure that remains high despite treatment with current medications. The Challenge provides resources for small-molecule discovery and offers the opportunity for long-term collaboration. Continue reading “Sanford-Burnham wins GlaxoSmithKline drug discovery challenge”

Institute News

Using geometry to design new drugs

Authorsgammon
Date

November 19, 2014

In a new study published in ACS Chemical Biology, Sanford-Burnham’s Stefan Riedl and Elena Pasquale created a molecule with an improved ability to block the activation of a cell receptor called EphA4. When EphA4 is activated, it can hinder the ability of neurons to repair themselves and exacerbates certain degenerative processes, such as amyotrophic lateral sclerosis (ALS)—often referred to as Lou Gehrig’s Disease; Alzheimer’s disease; and stroke. The molecule is a cyclic peptide that represents a promising therapeutic lead for targeting neurodegenerative diseases and some cancers. Continue reading “Using geometry to design new drugs”

Institute News

Join us for the second cancer center open house – November 6

Authorrbruni
Date

October 27, 2014

Sanford-Burnham’s NCI-Designated Cancer Center and the Cancer Center’s Community Advisory Board will host the second annual Cancer Center open house for cancer survivors, their families and friends, and research advocates on November 6 at 4:30 p.m. in La Jolla, Calif. Continue reading “Join us for the second cancer center open house – November 6”

Institute News

Unique pathway that homes cancer drugs to tumors is like no other

Authorsgammon
Date

October 3, 2014

In a new study published in Nature CommunicationsErkki Ruoslahti, MD, Ph.D., and his research team, with Hongbo Pang, PhD, as the lead author, identify the unique pathway that enhances the delivery of anti-cancer drugs to tumors. The pathway, called CendR, is a previously unknown variation of endocytosis—the process by which cells engulf nutrients and extracellular molecules. When activated, the CendR system improves the therapeutic efficacy of existing anti-cancer drugs while minimizing the collateral damage of normal cells and tissue. The findings advance our understanding of the biology of the cell by establishing a new type of trans-tissue transport pathway. Continue reading “Unique pathway that homes cancer drugs to tumors is like no other”