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Friday, January 4, 2019

Poseida Therapeutics Prepares for IPO to Advance CAR-T Treatments


Poseida Therapeutics, which is testing CAR-T cell therapies for blood-borne and solid tumor cancers, has laid the groundwork for an initial public offering.
In documents filed with securities regulators Friday, the San Diego company set a preliminary IPO target of $115 million. The company has applied for a listing on the Nasdaq stock exchange under the symbol “PSTX.”
CAR-T therapies deploy T cells that have been engineered to kill cancer. These cells, programmed to act aggressively, have in some cases led to significant side effects, however. Results for the first two CAR-T products approved, both in 2017, have varied.
Poseida said its treatments are intended to address the challenges of early-generation CAR-T therapies, including duration, tolerability, and scalability.
The company said it plans to use the IPO proceeds to continue funding clinical development of its lead drug candidate, an CAR-T product for relapsed/refractory multiple myeloma, and to continue developing its preclinical drug candidates and research. It may also use some of the money to start a pilot manufacturing facility, which would cost as much as $15 million, Poseida said in the filing.
Poseida’s lead candidate, P-BCMA-101, is in Phase 1 testing. The investigational drug is targeting BCMA, a protein found on the surface of cancerous B cells in the bone marrow. The study is funded in part by the California Institute for Regenerative Medicine. Poseida said it plans to move the therapy into a Phase 2 trial by June.
It is also developing a CAR-T product candidate using cells from a healthy donor rather than the patient—a so-called autologous therapy. Poseida said it aims to make and store the candidate, P-BCMA-ALLO1, for future use. If all goes as planned, it will enter Phase 1 testing by early 2020, the company said.
Another autologous therapy Poseida is developing, P-PSMA-101, is being developed for patients with a form of prostate cancer that continues to spread even after a patient’s testosterone levels have been significantly reduced. The company said it plans to begin Phase 1 testing of P-PSMA-101 in the second half of this year. And P-MUC1C-101, another CAR-T that uses a patient’s own cells, is in late-stage preclinical development for multiple solid tumor cancers. That could enter clinical testing in 2020, the company said.
Even if Poseida meets its goal and raises $115 million in the IPO, eventually it will have to raise additional cash, according to the filing.
Poseida is headed by CEO Eric Ostertag. He founded Kentucky-based gene editing technology company Transposagen, which Poseida was spun out from in 2015. The company has since raised $74.8 million, borrowed $20 million, and received $15 million of a total $23.8 million awarded in grant funding from the California Institute of Regenerative Medicine, according to regulatory documents.
The company reported net losses of $19.7 million in 2017 and $31.5 million in the first nine months of 2018.
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December saw the most new healthcare hires in decades


December brought the U.S. healthcare industry’s largest monthly spike in the number of new hires since at least February 1990.
Healthcare added 50,200 jobs last month, the largest numeric increase in new hires in Modern Healthcare’s monthly jobs data, which stretches back to February 1990. Hiring in the industry jumped 56% from November, according to the U.S. Bureau of Labor Statistics’ December jobs report released Friday. The last time healthcare hiring surpassed 40,000 in a single month was in October 2015, the data show.
While more than 50,000 new jobs was “an unexpectedly high number,” healthcare hiring has grown at higher rates in the recent past, said Ani Turner, co-director of sustainable health spending strategies with the consultancy Altarum. The healthcare jobs growth rate hit 2.2% in December, beating out the non-healthcare growth rate of 1.7%.
Turner said she expected healthcare hiring to level off at the end of the year rather than to increase further, especially given the fact that insurance coverage expansion has largely plateaued. It could be just the normal monthly fluctuation in jobs numbers.
“Sometimes the numbers do kind of bounce up and down,” Turner said.
Healthcare’s share of total jobs rose to an all-time high of 10.79% in December. That’s partly because healthcare continued to grow and add jobs during the Great Recession, even as the rest of the economy lost jobs and took a long time to regain them.
“It stays steady and continues to grow while everything else bottoms out,” Turner said.
Three-quarters of the new healthcare hires were in the ambulatory sector, adding 37,800 jobs in December, 97% more than in November. Within ambulatory, home health comprised the biggest increase, adding 13,300 jobs, up more than 230% from November. Dentists’ offices added 7,200 jobs, compared with just 300 in November. Physicians’ offices made 6,700 new hires, up 22% from November. Outpatient care centers added 3,100 jobs, down 47% from November.
It’s unclear why home health saw such a dramatic spike in December. Sometimes consumers who have met their insurance deductibles seek more care at the end of the year, but that doesn’t necessarily translate into more hiring, and especially not for home health providers, Turner said.
“I would not be at all surprised to see a very low number in home health next month,” she said. “Sometimes it just does fluctuate like that.”
December wasn’t a stellar month for hospitals, however, which added 7,400 jobs last month, down 42% from their November total of 12,700.
Residential mental health facilities added 2,900 jobs last month, an improvement from November, in which they lost 900 jobs. Nursing care facilities experienced a December lull in hiring, adding 700 jobs, down from 900 new hires in November. Community care facilities for the elderly added only 100 jobs.
Total nonfarm employment rose by 312,000 jobs in December, and the unemployment rate rose by 0.2 percentage points to 3.9% as more people looked for work.
Healthcare added more jobs than any other industry last month. It beat out professional and business services, which added 43,000 jobs, and food services and drinking places, which added 41,000.
Overall in 2018, healthcare added 346,000 jobs, more than the 284,000 jobs added in the industry in 2017.
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Creating New and Better Habits for the New Year


Recently, Mike Bellafiore at SMB Capital has been emphasizing the idea of positive habit formation with his traders.  It’s a great focus for the new year:  developing the patterns of thought and behavior that help us achieve our goals.  Here’s an excellent video from James Clear, based on his new book,Atomic Habits.  An important point made by the video is that we can transform our experience of ourselves one small behavior at a time, as we internalize whatever it is that we do.  Of course, that can also work in reverse:  when we fall into bad habits, we can internalize the sense of being lazy, unproductive, undisciplined, etc.
Here’s an interesting video from Tony Robbins that connects changes in our behavior to changes in our emotional and physical states.  The implication is that we don’t have to repeat the common pattern of making new year’s resolutions, only to see them fall by the wayside.  We can use our emotional and physical states to trigger the right behaviors and we can change our behaviors to form new and powerful habit patterns.
In the book that I am currently writing, I describe how the great spiritual traditions of the world provide us with powerful tools for changing our states and accessing our strengths.  This has important implications for traders:  the great trades come from the soul, not the ego.  In developing ourselves spiritually, we can find greater success in the material world.  This is because we move beyond ego-based motivations and reactionsand more consistently access who we truly are.
In short, we will not transform our trading by staring at screens, hanging on each tick of profit or loss.  We will not transform our trading by pushing, pushing, pushing to get bigger, bigger, bigger in our trades.  Nor will we transform our trading by focusing on every move that we don’t monetize.
Spirituality, too, can become a habit.  Lots of good things can happen when our best practices and greatest strengths become our consistent processes.
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California high court won’t review $91M fine against UnitedHealthcare


The California Supreme Court says it won’t review a lower court’s decision last year that set the stage for Minnetonka-based UnitedHealth Group paying a $91 millionfine to the state’s insurance commissioner.
In September, an appeals court ruled in favor of California regulators in their attempt to impose fines on a UnitedHealth subsidiary called PacifiCare related to more than 900,000 alleged violations of state law on insurance claims.
After the ruling, UnitedHealth said it would appeal the matter to the California Supreme Court, but the court late Thursday said it would not review the case.
“I am delighted the Supreme Court has rejected further challenges to the insurance commissioner’s authority to punish insurance companies for knowingly harming even one consumer,” said Dave Jones, the California Insurance Commissioner, in a statement on Friday.
UnitedHealth Group on Friday did not immediately provide a statement in response.
In 2005, UnitedHealth Group acquired PacifiCare for $9.2 billion in a deal that was one of the biggest health plan mergers at the time. Two years later, UnitedHealth Groupofficials acknowledged in an unusual public confession that the company had forced new technology and business practices too quickly in new markets such as California, resulting in “physician resentment, network disruptions and operational overload.”
UnitedHealth pledged to pay claims faster and repair relationships with doctors, and the California Medical Association told the Star Tribune in 2010 that PacifiCare seemed to have solved problems. The California Department of Insurance in 2008 filed an enforcement action against PacifiCare, alleging the insurer engaged in multiple unfair claims settlement practices and other violations of the insurance code. Following a hearing, the insurance commissioner found PacifiCare engaged in over 900,000 acts and practices in violation of the code.
“Customers have no choice but to rely on the integrity of their health insurance companies,” Jones said in a statement. “PacifiCare breached that trust.”
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Select Medical Holdings Corporation: Announces Business Outlook for 2019


Select Medical Holdings Corporation (“Select Medical”) (NYSE: SEM), today announced its business outlook for calendar year 2019.
Select Medical expects consolidated net operating revenues for the full year 2019 to be in the range of $5.2 billion to $5.4 billion.  Select Medical expects net income before interest, income taxes, depreciation and amortization, stock compensation expense, other income/(expense), and equity in earnings/(losses), or Adjusted EBITDA for the full year 2019 to be in the range of $660 million to $700 million.  Select Medical expects fully diluted income per common share for the full year 2019 to be in the range of $0.97 to $1.13.
Select Medical assumed a 25.5% effective tax rate when preparing the above business outlook for 2019. Select Medical assumed total shares outstanding of 135 million when preparing the above business outlook for 2019. This share count includes unvested restricted shares, which have participation rights and are allocated an equitable portion of earnings under the two-class method for calculating income per common share.
The following is a reconciliation of full year 2019 Adjusted EBITDA expectations as computed to the low and high points of the range to the closet comparable GAAP financial measure.  Refer to Select Medical’s most recent Form 10-Q filing for a discussion of Select Medical’s use of Adjusted EBITDA in evaluating financial performance and determining resource allocation.  Each item presented in the table below is an estimation of full year 2019 expectations (dollars in millions).
Range
Non-GAAP Measure Reconciliation
Low
High
Net Income attributable to Select Medical
$             132
$             153
Net Income attributable to non-controlling interests
56
65
Net Income
188
218
Income tax expense
64
74
Interest expense
200
200
Equity in earnings of unconsolidated subsidiaries
(25)
(25)
Income from operations
427
467
Stock compensation expense
27
27
Depreciation and amortization
206
206
Adjusted EBITDA
$             660
$             700
Select Medical is one of the largest operators of critical illness recovery hospitals (previously referred to as long term acute care hospitals), rehabilitation hospitals (previously referred to as inpatient rehabilitation facilities), outpatient rehabilitation clinics, and occupational health centers in the United States based on the number of facilities. Our reportable segments include the critical illness recovery hospital segment, rehabilitation hospital segment, outpatient rehabilitation segment, and Concentra segment. As of September 30, 2018, Select Medical operated 97 critical illness recovery hospitals in 27 states, 26 rehabilitation hospitals in 11 states, and 1,649 outpatient rehabilitation clinics in 37 states and the District of Columbia. Select Medical’s joint venture subsidiary Concentra operated 525 occupational health centers in 41 states. Concentra also provides contract services at employer worksites and Department of Veterans Affairs community-based outpatient clinics. At September 30, 2018, Select Medical had operations in 47 states and the District of Columbia. Information about Select Medical is available at www.selectmedical.com.
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Low-Dose Amitriptyline Effective for Chronic Low Back Pain


Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain: A Randomized Clinical Trial

Urquhart DM, Wluka AE, van Tulder M, et al
JAMA Intern Med. 2018;178:1474-1481

Study Summary

The largest contributor to global disability is low back pain, for which various treatments are available but are of limited efficacy. International clinical guidelines recommend low-dose antidepressants for management of chronic low back pain, and these are often prescribed for this widespread condition. To date, however, there has been no evidence that they are effective for this indication.
The goal of this double-blind, randomized clinical trial was to compare the efficacy of 6 months of treatment with a low-dose antidepressant (amitriptyline, 25 mg/day) versus an active comparator (benztropine mesylate, 1 mg/day) in reducing pain, disability, and work absence and interference in adults with chronic, nonspecific low back pain.
Participants (n = 146; mean age, 54.8 ± 13.7 years; 61.6% male) were recruited from hospital/medical clinics and through advertising. Pain intensity at 3 and 6 months was measured with the visual analogue scale, and the Descriptor Differential Scale was the primary outcome. The Roland Morris Disability Questionnaire and the Short Form-Health and Labour Questionnaire were used to determine secondary outcomes of disability and work absence and interference.
Among 118 participants (81%) who completed 6-month follow-up, pain reduction with low-dose amitriptyline or the comparator did not differ significantly at 6 months (adjusted difference, -7.81; 95% confidence interval [CI], -15.7 to 0.10) or at 3 months (-1.05; 95% CI, -7.87 to 5.78), independent of baseline pain. The low-dose amitriptyline group versus the comparator group had a statistically significantly better improvement in disability at 3 months (adjusted difference, -1.62; 95% CI, -2.88 to -0.36), but not at 6 months (-0.98; 95% CI, -2.42 to 0.46). Work outcomes of absence or hindrance at 6 months or 3 months and the number of participants who withdrew because of adverse events (12%) did not differ significantly between the groups.

Viewpoint

This trial is limited by the heterogeneity of patients with chronic, nonspecific low back pain and its possibly insufficient power to detect differences in work or additional outcomes. Nonetheless, this first double-blind, randomized controlled trial of a low-dose tricyclic antidepressant for this condition suggests that it may be effective. Compared with an active agent, low-dose amitriptyline was associated with a reduction in disability at 3 months and a nonsignificant improvement in pain intensity at 6 months. The two treatments appeared to be equally well tolerated and effective for pain relief.
The findings merit further testing in large-scale randomized trials that include dose escalation. Given the global opioid overuse epidemic, clinicians may find it useful to consider low-dose amitriptyline while awaiting these results, particularly if the only alternative is opioids.
Low-dose amitriptyline has been shown to be effective in other pain conditions, and its off-label prescription for low back pain is rapidly increasing. Because low back pain management focuses on progressively increasing activity levels, low-dose amitriptyline may be relevant to overall therapy by reducing pain, disability, and fear, which are important barriers to activity.
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Cognitive Risks Tied to High Blood Pressure Brain Changes


Changes in periventricular white matter hyperintensities (WMH) accompanied development of mild cognitive impairment in adults with hypertension, a longitudinal population-based study in Spain found.
Hypertensive older adults who showed a marked progression of periventricular WMH had a sixfold risk of incident mild cognitive impairment compared with patients without this progression (OR 6.184, 95% CI 1.506-25.370, P=0.011), according to Pilar Delgado Martinez, MD, PhD, of the Institut de Recerca Hospital Vall d’Hebron in Barcelona, and colleagues.
These patients also demonstrated a significant decrease in global cognition (adjusted mean -0.519 ± 0.176 vs 0.057 ± 0.044, P=0.004), the team reported in Hypertension.
Finding new ways to detect cognitive impairment may help identify who is at risk for dementia, the authors noted. “As patients with hypertension are at high risk for cerebral small vessel disease progression, the identification of specific lesions that have higher odds of impairing cognition may have useful implications in clinical practice.”
The study builds upon prior research about cerebral small vessel disease and cognitive function, noted Ilya Nasrallah, MD, PhD, of the University of Pennsylvania in Philadelphia, who was not involved with the study.
“Understanding the link between small vessel disease and cognition is important because we are currently able to alter the course of small vessel disease,” Nasrallah told MedPage Today. “In the SPRINT study, for example, we showed that intensive treatment of hypertension to <120 mm Hg systolic resulted in lower incident mild cognitive impairment and lower progression of cerebral white matter lesions.”
In the Barcelona study, the researchers followed 345 hypertensive men and women in the ISSYS (Investigating Silent Strokes in Hypertensives: A Magnetic Resonance Imaging Study) cohort, an ongoing epidemiological, observational study. At baseline (from 2010 to 2012), participants were a median age of 65 and had no previous dementia or stroke. Most — 94.2% — were being treated for hypertension and 55.4% were male.
Mean follow-up was 3.95 years and average blood pressure at follow-up was 144.5/76.5 mm Hg.
At baseline and follow-up, patients underwent evaluations that included brain MRI and cognitive testing. The researchers used the Dementia Rating Scale 2nd version (DRS-2) to assess a general measure of cognitive function, and asked participants whose DRS-2 scores suggested cognitive impairment to undergo a second evaluation to establish a cognitive diagnosis. They qualitatively defined MRI changes in periventricular white matter hyperintensities and deep white matter hyperintensities as “none,” “minor,” or “marked.”
During the study, 9.1% of participants developed mild cognitive impairment. Incident lacunar infarcts occurred in 6.1% of participants and cerebral microbleeds in 5.5%. Minor or marked periventricular WMH progression appeared in 22% of patients and deep WMH progression occurred in 48%.
Only marked progression of periventricular WMH was associated with incident mild cognitive decline; changes in deep WMH, incident infarcts, and cerebral microbleeds were not tied to incident cognitive impairment. Incident cerebral microbleeds, however, were tied to a decline in attention.
“This study confirms previous observations on the effects of hypertension on brain vasculature and cognitive function in elderly individuals,” observed Oscar Lopez, MD, of the University of Pittsburgh, who was not involved with the research. “It emphasizes the importance of a strict adherence to antihypertensive treatments,” he told MedPage Today.
The researchers noted several limitations to their study. Due to budget constraints, patients were selected for follow-up based on the severity of baseline cerebral small vessel disease, so results may not apply to all patients with hypertension. Volumetric approaches to measuring MRI changes in hyperintensities would have been more precise than qualitative assessments. The team also did not include neurodegeneration markers like tau or amyloid-beta which may be related to hypertension and cerebral small vessel disease lesions.
This research was funded by the Instituto de Salud Carlos III and AGAUR, with the support of the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund.
The researchers reported no disclosures.
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