IND-enabling activities initiated for EDIT-301, a potentially best-in-class experimental medicine for the treatment of sickle cell disease and beta-thalassemia
Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today announced results from a follow-up study to assess two different CRISPR genome editing strategies, one targeting the BCL11A erythroid enhancer (BC11Ae) and one targeting the beta-globin locus, for the treatment of sickle cell disease and beta-thalassemia. The Company reported the data at the 24th Congress of the European Hematology Association in Amsterdam.
In this study, NBSGW mice received an infusion of human CD34+ cells which had been edited either at the BCL11Ae or at the beta-globin locus. In vivo-derived erythroid cells from BCL11Ae-edited CD34+ hematopoietic stem/progenitor cells had reduced total indels and increased non-productive indels as compared to other tested lineages, a phenomenon not observed with beta-globin locus editing. Additionally, further optimization of nuclease and guide RNA combinations led to fetal hemoglobin expression of approximately 40 percent in the beta-globin locus-edited erythroid cells. Based on the data, Editas Medicine has initiated IND-enabling activities for EDIT-301, an experimental CRISPR medicine designed to durably treat sickle cell disease and beta-thalassemia by editing the beta-globin locus.
“We are encouraged by these pre-clinical results demonstrating cells edited at the beta-globin locus repopulated all lineages of the blood system including, importantly, the red blood cell precursors and the high percentage of fetal hemoglobin expression. Editing at this site continues to meet our preclinical goals for making a medicine including robust, long-term induction of fetal hemoglobin and maintenance of normal hematopoietic stem/progenitor cell function,” said Charles Albright, Ph.D., Chief Scientific Officer, Editas Medicine. “Our program is on track towards the clinic, and we have started our IND-enabling activities as we look to develop a best-in-class medicine for the treatment of sickle cell disease and beta-thalassemia.”
For biotech stocks, the week was back loaded with multiple conferences scheduled for the later half of the week. Nevertheless, there were volatile moves in some low-float, thinly traded stocks.
Looking ahead, keep an eye on the following key catalysts.
Conferences
The Annual European Congress of Rheumatology of the European League Against Rheumatism – June 12-16, in Switzerland
24th European Hematology Association Congress – June 13-16, in Amsterdam, Netherlands
European Society of Human Genetics Conference – June 15-18, in Gothenburg, Sweden
The International Association of Parkinson’s Disease and Related Disorders (IAPR) World Congress on Parkinson’s Disease and Related Disorders – June 16-19, Montreal, Canada
5th International Conference on Influenza and Zoonotic Diseases – June 17-18, in Berlin, Germany
9th World Congress on Rare Diseases and Orphan Drugs – June 17-18, in Berlin
International Conference On Malignant Lymphoma – June 18-20, in Switzerland
Oxalosis Hyperoxaluria Foundation, or OHF, International Hyperoxaluria Workshop – June 21-22, in Boston, Massachusetts
PDUFA Dates
The FDA is set to rule on Merck & Co., Inc. MRK 0.19%‘s sBLA in Keytruda for treating patients with advanced small cell lung cancer, whose disease has progressed after two or more lines of prior therapy. The PDUFA date is scheduled for Monday, June 17.
Clinical Trial Readouts
ArQule, Inc. ARQL 30.21% is scheduled to present Phase 1/2 data for ARQ 092 to treat overgrowth diseases at the European Society of Human Genetics Conference June 17.
Affimed NV AFMD 3.77% will present updated Phase 1b/2a data for AFM13 in CD30-postive lymphoma at the International Conference On Malignant Lymphoma June 17. The company will also present updated Phase 1b data for AFM13 with Merck’s Keytruda in Hodgkin’s Lymphoma at the same conference Saturday, June 22.
Beigene Ltd . BGNE 6.04% will present updated Phase 2 data for its Zanubrutinib in relapsed or refractory mantle cell lymphoma at the International Conference On Malignant Lymphoma Wednesday, June 19. The company will also present Phase 1b data for Zanubrutinib and Obinutuzumab in relapsed/refractory follicular lymphoma at the International Conference On Malignant Lymphoma Thursday, June 20.
Epizyme Inc . EPZM 3.21% is due to present updated Phase 2 data for its Tazemetostat in follicular lymphoma at the International Conference On Malignant Lymphoma Friday, June 21.
Morphosys Ag MOR 0.4% will present already-released Phase 2 data for Lenalidomide + MOR208 in relapsed or refractory diffuse large B cell lymphoma at the International Conference On Malignant Lymphoma, Saturday, June 22.
Theravance Biopharma Inc TBPH 5.01% is set to release Phase 2, 5-month data for its Ampreloxetine in nOH at the IAPRD 2019 World Congress on Parkinson’s Disease and Related Disorders to be held between June 16-19.
Allena Pharmaceuticals Inc ALNA 5.11% will present detailed Phase 2 data for Reloxaliase ALLN-177 in primary hyperoxaluria at the OHF International Hyperoxaluria Workshop to be held between June 21-22.
IPOs
Akero Therapeutics, which develops therapies for NASH and other metabolic disorders, is scheduled to offer 5 million shares in an IPO, to be priced between $14 and $16. The company seeks to list the shares on the Nasdaq under the ticker symbol AKRO.
Atreca proposes to offer 7.35 million shares in an IPO, with the price estimated in the range of $16-$18. The shares of the company developing therapies for solid tumors are likely to be listed on the Nasdaq under the ticker symbol BCEL.
Dermatological-disease focused Dermavant Sciences will offer 7.7 million shares in an IPO to be priced in the range of $12-$14. The company seeks a Nasdaq listing under the ticker symbol DRMT.
Genomic sequencing company Personalis is targeting a Nasdaq listing under the ticker symbol PSNL, by offering 6.67 million shares in the price range of $14-$16.
Prevail Therapeutics is scheduled to offer 7.352 million shares in an IPO, with the price estimated to be $16-$18. The shares would be listed on the Nasdaq under the ticker symbol PRVL.
Stoke Therapeutics, which develops RNA-targeted therapies for rare genetic disorders has planned a 6.7-million share IPO, to be priced between $14 and $16. The company proposes to list the shares on the Nasdaq under the ticker symbol STOK.
Children who are vaccinated against the virus that causes chickenpox are getting a twofer: Not only are they protected against irritating and potentially scarring chickenpox, but they appear to have a “dramatically” lower risk of developing shingles in childhood than unvaccinated kids who contract the disease, according to a large, new multiyear study.
The rate of shingles cases in vaccinated children was 78% lower than it was among unvaccinated children who had contracted the virus, varicella, the authors reported Monday in the journal Pediatrics.
Overall over the 12-year period studied, the rate of shingles cases among all children in the study fell by 72%, as increasing numbers of vaccinated children likely led to a decrease in infections among unvaccinated children through a phenomenon called herd immunity.
As the amount of immunity against a pathogen like the varicella virus grows in a given population, it becomes harder for the virus to find and infect children who aren’t vaccinated.
“So the vaccine is not only preventing chickenpox, but there’s an added benefit thrown in that we had hoped would happen,” said Dr. Anne Gershon, a pediatric infectious diseases professor at Columbia University, said of the finding of reductions in shingles cases among children.
Gershon was not involved in the research, but she wrote a commentary on it that the journal published in conjunction with the study. “That the varicella vaccine prevents not only varicella but zoster as well is an exciting dual benefit from the varicella vaccine, further improving the health of children by immunization,” she wrote. Herpes zoster is the proper name for shingles.
The study, which was funded by the Centers for Disease Control and Prevention, mined the medical records of more than 6 million children to try to tease out an answer of whether the varicella vaccine would protect against shingles, or potentially increase the risk of developing the painful condition.
Shingles is a delayed complication of varicella infection. The virus hides in the body of people who have had chickenpox. Normally the immune system keeps it in check. But the virus can reactivate, causing painful rashes that can lead to long-term nerve pain. It is estimated that about one-third of people who had chickenpox will go on to have at least one bout of shingles.
While the condition is more common in older adults whose immune systems are waning, children too can develop shingles.
The varicella vaccine is made with a live but weakened varicella virus, which can also lie dormant and later reactivate to cause shingles.
In 2013, the authors of the current study published an earlier investigation of shingles rates among vaccinated children. They found a substantially lower rate among vaccinated children overall, but a significantly higher rate among children between the ages of 1 (around the time the first dose of two doses of vaccine is given) and 2.
They set out to dig further into that finding. Lead author Sheila Weinmann, senior investigator with Kaiser Permanente Northwest Center for Health Research, said they felt it was important to find out what was going on.
The first study followed 322 children for four years. For the second study, the group looked at medical records of nearly 6.4 million children under the age of 18, calculating rates of shingles over 12 years.
They did see a higher rate of shingles among vaccinated 1-year olds as compared to unvaccinated children. But that difference quickly reversed. Among 2- and 3-year olds, there wasn’t really a marked difference between the vaccinated and unvaccinated children. By age 4, the rates of shingles among unvaccinated children started to climb; among vaccinated children, it declined slightly and then remained at a low and relatively stable rate.
The reason for the earlier shingles rate among 1-year-olds? They were being exposed to varicella virus before the unvaccinated children were. “If they hadn’t ever had chickenpox then they weren’t going to be likely to get shingles,” Weinmann said of the unvaccinated 1-year olds.
But given the highly infectious nature of the varicella virus, that quickly changed, as the rates among older unvaccinated children showed. In the era before the varicella vaccine came on the market, virtually everyone contracted chickenpox in childhood; the CDC estimated that every year about 4 million children were infected.
So among older unvaccinated children, shingles rates rose after chickenpox infections. Overall there were 38 cases of shingles per 100,000 person years in the vaccinated group, compared to 170 cases per 100,000 person years among the unvaccinated children.
Whether the vaccinated children will continue to have lower rates of shingles as they move into the later stages of life remains to be seen, Gershon said, as does whether those vaccinated in childhood will need a varicella booster vaccine at some point in adulthood.
Taylor found these bag bans did what they were supposed to: People in the cities with the bans used fewer plastic bags, which led to about 40 million fewer pounds of plastic trash per year. But people who used to reuse their shopping bags for other purposes, like picking up dog poop or lining trash bins, still needed bags. “What I found was that sales of garbage bags actually skyrocketed after plastic grocery bags were banned,” she says. This was particularly the case for small, 4-gallon bags, which saw a 120 percent increase in sales after bans went into effect.
Trash bags are thick and use more plastic than typical shopping bags. “So about 30 percent of the plastic that was eliminated by the ban comes back in the form of thicker garbage bags,” Taylor says. On top of that, cities that banned plastic bags saw a surge in the use of paper bags, which she estimates resulted in about 80 million pounds of extra paper trash per year.
The waste issue is better, but paper bag production increases carbon emissions. And tote bags, particularly those made from cotton, aren’t great either.
The Danish government recently did a study that took into account environmental impacts beyond simply greenhouse gas emissions, including water use, damage to ecosystems and air pollution. These factors make cloth bags even worse. They estimate you would have to use an organic cotton bag 20,000 times more than a plastic grocery bag to make using it better for the environment.
A new University of Michigan study challenges a popularized view about what’s causing the growing gap between the lifespans of more- and less-educated Americans–finding shortcomings in the widespread narrative that the United States is facing an epidemic of “despair.”
Some influential studies have argued that growing life expectancy inequality is driven by so-called “deaths of despair,” suggesting that economic stagnation has induced less-educated Americans to turn to drugs, alcohol and suicide.
Yet, that explanation is inconsistent with a large body of research on the way many disadvantaged Americans respond to stress, says Arline Geronimus, a professor at U-M’s School of Public Health and lead author of the study published in the June issue of the Journal of Health and Social Behavior.
“The assumption that people are giving up neglects the existing research that shows the engaged and tenacious ways people often deal with life challenges,” Geronimus said.
Geronimus and her team set out to look at whether the empirical data backed this concept. They used Census and Vital Statistics data to evaluate historically relevant causes of deaths–including opioids, cardiovascular disease, HIV, and lung or other cancers–for non-Hispanic blacks and whites between 1990 and 2015, ranking them by gender and education (less or more educated).
When looking at the deaths of despair (drug overdose, suicide and alcohol-related liver diseases), the researchers found that drug overdoses do contribute to the widening inequality for whites, especially men, but that’s not the case for blacks. Also, they found that overdose deaths are less important for growing inequality in women’s life expectancy.
For older adults, where the growth in inequality is largest, premature death due to cardiovascular disease and cancers are the main reason for the widening gap–not overdose deaths. The early onset and progression of such chronic diseases can reflect the physiological impact of prolonged and resolute coping with life stressors, Geronimus says.
She points out that suicide rates have contributed little to the growing inequality gap, contrary to the “deaths of despair” theory. Instead, deaths due to cardiovascular disease, non-lung cancers and other internal diseases might help explain important shares of the growing life expectancy gap between those less educated and their highly educated counterparts, Geronimus says.
“These findings suggest that, rather than giving up in the face of hopelessness, less-educated Americans may be losing ground for exactly the opposite reason–because they work so hard, they bear the health consequences of years of stress,” she said.
As for the opioid epidemic, Geronimus says researchers should also consider how targeted marketing to white populations, overprescription of legal opioids by physicians, the increasing use of fentanyl in street drugs, and restricted access to life-saving resources have all contributed to the increase in inequality in life expectancy accounted for by opioid deaths in whites.
“The deaths of despair narrative is speculative, overlooks black lives and implies that lack of resilience explains the life expectancy inequities among whites, especially of those who have been socioeconomically disenfranchised,” Geronimus said.
“While addressing the opioid epidemic is urgent, we should not lose sight of the widening educational mortality gap attributed to cardiovascular disease, cancers and other internal causes.”
As BeiGene sets the stage for a pivotal showdown with the OG BTK inhibitor Imbruvica, its zeroing in on a subset of patients for whom their drug, zanubrutinib, could be especially helpful.
The Chinese biotech also brandished the latest mid-stage results for its PD-1 drug visilizumab, another franchise shaker thats under priority review in China, at the EHA Congress.
Investigators took a data cut from a Phase III open-label trial that is putting zanubrutinib against Imbruvica (ibrutinib) in patients with Waldenstrms Macroglobulinemia to showcase promising response rates. A non-randomized cohort of 26 patients, who has the MYD88WT genotype of WM, all received zanubrutinib. Five of them were treatment-nave while the others had relapsed/refractory disease.
For these patients, who typically have poorer prognoses with lower response rates, we recognize the real need for a highly potent and selective BTK inhibitor that can sustain BTK inhibition and reduce off-target effects, CMO Jane Huang said in a statement.
At a median follow-up of 12.2 months, the drug scored an overall response rate of 80.8%, with 53.8% of patients experiencing a partial response or better. The very good partial response rate was 23.1% while exactly one patient achieved a complete response.
Imbruvica was first approved in 2015 as a monotherapy for WM, a rare, slow-growing and incurable form of non-Hodgkin lymphoma. A combination with Rituxan was also OKd last year based on progression-free survival results. The hazard ratio compared to Rituxan alone was an impressive 0.20 (p
Stemline Therapeutics, Inc. (STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, announced that ELZONRIS™ (tagraxofusp) is the subject of three clinical presentations at the Congress of the European Hematology Association (EHA). Data from the ongoing Phase 1/2 trials in chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), as well as the results from the pivotal trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN) will be delivered via poster presentation at the 24th Congress of the European Hematology Association (EHA) in Amsterdam, Netherlands.
ELZONRIS (tagraxofusp) is FDA-approved for the treatment of patients, adults and pediatric 2 years and older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN), and is commercially available in the U.S.
Presentations will be available on the Stemline website (www.stemline.com) Scientific Presentations tab, after their delivery.
