Daily Archives: January 13, 2022

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It may sound like something out of utopian sci-fi, but a prominent futurist says were not too far off from breaking the genetic mold that has until now comprised the building blocks of human life.

In a wide-ranging interview withThe Washington Post, futurist Amy Webb predicted that the science of procreation will significantly change the way we have babies and may even change the maximum number of biological parents a person can have.

What were talking about here is a technology that unlocks our ability to be more selective and to intentionally design life, said Webb, discussing her new book The Genesis Machine, co-written with geneticist Andrew Hessel. Maybe that means one person using their own genetic material to bring an embryo to term; maybe it unlocks opportunities to select traits from more than two parents.

The author and founder of the Future Today Institute consulting firm admitted that while scientists and futuristic soothsayers like herself dont yet know the full applications for gene editing technology like CRISPR and others that are sure to follow, she believes the possibilities and optionality that could soon be afforded those who decide to procreate could be significant and a net good.

As always, the question of genetic engineering often leads directly to discussions of the potential for governmental abuse. But Webb dismissed those concerns, quipping to WaPo thatall roads on this path lead to eugenics name-checking the 1997 sci-fi flickGattaca.

While those for whom future is their business need to acknowledge the geopolitical advantages that some countries might try for by elevating their populations intelligence and physical traits, that doesnt mean we should reject synthetic biology wholesale, Webb suggested.

The thought of making pregnancy easier for people who really want to become parents is something we should be embracing, she told WaPo. Right now, creating a child relies on chance and serendipity, or enough money for a lot of [in-vitro fertilization] cycles. Its shockingly difficult in the year 2022 to make a baby. It shouldnt be that way.

Its an exciting prospect indeed, especially considering how prevalent maternal illness and even death can be in general and for mothers of color in particular.

Theres no reason not to imagine, design, and fund technology that will make getting pregnant, carrying fetuses to term, and giving birth as safe as, say, getting cosmetic surgery and with that kind of tech within our grasp, the sky is literally the limit when it comes to how reproductive science will look decades down the road.

READ MORE:Futurist Amy Webb says babymaking could get crazy and the smartphone will die [The Washington Post]

More on our not-so-distant genetic futures: Could We Gene Hack Ourselves to Be Blissed Out Sex Maniacs, Like Our Distant Cousins the Bonobos?

Care about supporting clean energy adoption? Find out how much money (and planet!) you could save by switching to solar power at UnderstandSolar.com. By signing up through this link, Futurism.com may receive a small commission.

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Expert Says Children Will Soon Have More than Two Biological Parents - Futurism

Company provides summary business update and 2022 preview

SAN DIEGO, Jan. 10, 2022 /PRNewswire/ -- Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, today announced the appointment of Eric Ostertag as Executive Chairman and the transition of current President and Chief Business Officer, Mark Gergen, to the role of Chief Executive Officer effective as of February 1, 2022. The Company also provided a summary business update and 2022 preview.

Poseida Therapeutics (PRNewsfoto/Poseida Therapeutics, Inc.)

Poseida announces President Mark Gergen to serve as CEO, effective 2/1. Eric Ostertag named Executive Chairman. $PSTX

"For the last four years, Mark and I have worked closely to build Poseida into the organization it is today, making tremendous progress on a wide variety of initiatives which includes taking the company public in 2020, and preparing for the next wave of growth that lies ahead," said Eric Ostertag, M.D., Ph.D., Chief Executive Officer of Poseida Therapeutics. "Going forward, Mark will assume the overall leadership of the company while I will focus on high-level strategy, intended to maximize the value of our differentiated genetic engineering platforms and product candidates. In addition to continuing to chair the board of directors, I will also work to expand and further develop our scientific advisory boards."

As Poseida's founder and CEO, Ostertag directed the Company's spin out in early 2015 from parent company Transposagen Biopharmaceuticals, Inc., a biotechnology company that commercialized gene editing technology in research applications. Ostertag also founded Transposagen, where he was CEO from 2003 to 2015. Ostertag earned his M.D. and Ph.D. from the University of Pennsylvania. Under his leadership, Poseida grew to over 250 employees, raised significant private capital and successfully completed an IPO in 2020. The Company has also built a significant global intellectual property portfolio; received FDA clearance on four Investigational New Drug (IND) applications for novel cell therapies, dosing over 100 patients in clinical trials; and established multiple collaborations, including the recently announced gene therapy collaboration with Takeda Pharmaceutical Company Limited ("Takeda"), which has a potential total value of up to $3.6 billion.

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"It is a privilege to take on the role of CEO and lead the organization as we continue our progress toward our mission to redefine cell and gene therapy. The partnership Eric and I have built in guiding the company will continue," said Mark Gergen, Poseida's President and Chief Business Officer. "I am very excited about 2022 and the opportunities we will have to differentiate our platforms in both cell and gene therapy. We are highly focused on getting to key inflection points on our solid tumor and allogeneic CAR-T programs as well as advancing our gene therapy efforts, including those associated with our recent collaboration with Takeda."

Gergen joined Poseida in February 2018, serving as Chief Business Officer and Chief Financial Officer before being appointed President and Chief Business Officer in July 2020. During his career in the biotech and pharmaceutical industries, Gergen has provided strategic leadership to companies as they scale, grow, and execute on the promise of their technologies. Before joining Poseida, he held key leadership roles including that of Senior Vice President and Chief Operating Officer of Halozyme, Inc., Executive Vice President and Chief Operating Officer at Mirati Therapeutics, Inc. and as Senior Vice President of Corporate Development at Amylin Pharmaceuticals, Inc. He has also served in senior management positions at CardioNet Inc., Advanced Tissue Sciences, Inc., and Medtronic, Inc. Gergen received a J.D. from the University of Minnesota Law School and a B.A. in business administration from Minot State University in North Dakota.

Both Ostertag and Gergen will continue to serve as members of the Company's Board of Directors.

Business Update and 2022 Preview

Annual R&D DayThe Company will soon host its second annual R&D Day, scheduled for Wednesday, February 23, 2022. Dr. Ostertag will lead the event, featuring presentations highlighting the current product pipeline, advancements in early discovery and research programs, and detailing novel next generation approaches and technology applications. To register for the webcast, please visit the Investor Relations section of the Poseida website.

P-PSMA-101 Autologous CAR-T for Prostate CancerA Phase 1 trial evaluating P-PSMA-101, the Company's autologous CAR-T candidate for the treatment of metastatic castrate resistant prostate cancer (mCRPC) is ongoing. Initial clinical data was presented in late August 2021 at the CAR-TCR Summit demonstrating encouraging early results at low doses in this difficult to treat patient population with high unmet need. The Company will be presenting additional data during the ASCO Genitourinary Cancers Symposium taking place February 17-19, 2022, in a poster titled, "Phase 1 study of P-PSMA-101 CAR-T cells in patients with metastatic castration-resistant prostate cancer (mCRPC)."

P-BCMA-ALLO1 Allogeneic CAR-T for R/R Multiple MyelomaThe Phase 1 trial of P-BCMA-ALLO1, an allogeneic CAR-T product candidate for the treatment of relapsed refractory multiple myeloma, is currently initiating with a clinical data update expected later in the year. In addition to the continued product manufacturing at the current contract manufacturing organization, the Company is exploring a parallel path to enable manufacturing of P-BCMA-ALLO1 at its in-house GMP manufacturing pilot plant in San Diego, following successful manufacturing runs of the allogeneic CAR-T product candidate P-MUC1C-ALLO1.

P-MUC1C-ALLO1 Allogeneic CAR-T for Solid Tumors The Company announced on December 20, 2021 that the IND submitted for the P-MUC1C-ALLO1 product candidate had been cleared by the FDA. The Phase 1 clinical trial start-up is underway and will evaluate P-MUC1C-ALLO1 in various solid tumors, including breast, ovarian, lung and colorectal cancers. P-MUC1C-ALLO1 is manufactured at the Company's in-house GMP manufacturing pilot plant in San Diego. Initial clinical data from P-MUC1C-ALLO1 is expected to be presented at a scientific meeting this year.

Dual P-CD19CD20-ALLO1 Allogeneic Car T for B-cell MalignanciesDue to the prioritization of the lead allogeneic programs and the focus on achieving associated milestones in 2022, the Company is shifting expectations for an IND filing of its first dual CAR-T program from the end of 2022 into 2023.

P-OTC-101 In Vivo Liver Directed Gene Therapy for OTCThe Company's leading internal gene therapy program, P-OTC-101, an in vivo liver-directed gene therapy for ornithine transcarbamylase (OTC) deficiency, continues with IND enabling activities and evaluation of both a fully nanoparticle delivery approach as well as a hybrid nanoparticle/AAV approach. A decision of whether to pursue the fully nanoparticle or hybrid approach going forward is expected by mid-year.

Partnerships and CollaborationsThe Company's research collaboration with Takeda focused on nonviral in vivo liver- and HSC- directed gene therapies is underway. The collaboration, announced in October 2021, provides validation of Poseida's genetic engineering technology and approach. In 2022, the Company will continue to evaluate and explore additional opportunities for collaboration and partnership enabled by the breadth and versatility of the piggyBac, Cas-CLOVER, nanoparticle and other technology platforms.

About Poseida Therapeutics, Inc.Poseida Therapeutics is a clinical-stage biopharmaceutical company dedicated to utilizing our proprietary genetic engineering platform technologies to create next generation cell and gene therapeutics with the capacity to cure. We have discovered and are developing a broad portfolio of product candidates in a variety of indications based on our core proprietary platforms, including our non-viral piggyBac DNA Delivery System, Cas-CLOVER Site-specific Gene Editing System and nanoparticle- and AAV-based gene delivery technologies. Our core platform technologies have utility, either alone or in combination, across many cell and gene therapeutic modalities and enable us to engineer our portfolio of product candidates that are designed to overcome the primary limitations of current generation cell and gene therapeutics. To learn more, visit http://www.poseida.com and connect with us on Twitter and LinkedIn.

Forward-Looking StatementStatements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential benefits of Poseida's technology platforms and product candidates, Poseida's plans and strategy with respect to developing its technologies and product candidates, future roles and contributions of Poseida's executive officers, and anticipated timelines and milestones with respect to Poseida's development programs and manufacturing activities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon Poseida's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with development and regulatory approval of novel product candidates in the biopharmaceutical industry and the other risks described in Poseida's filings with the Securities and Exchange Commission. All forward-looking statement contained in this press release speak only as of the date on which they were made. Poseida undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Cision

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Poseida Therapeutics Announces Eric Ostertag to Serve as Executive Chairman and Transition Role of CEO to Current President and CBO Mark Gergen -...

Opaque land ownership rights engender corruption. Opposing organizations Greenpeace and Cato should unite in canvasing for the adoption of a blockchain register countering dead capital.

Greenpeace is one of the worlds most influential non-governmental organizations. With offices in 55 countries, several thousand staff, and a budget in the hundreds of millions of Euros range, it is committed to campaigning against climate change, deforestation, commercial whaling, genetic engineering and the nuclear industry.

The Cato Institute, by contrast, is much smaller: Just 100 staff (plus 46 faculty and 70 adjunct faculty) and an operating budget of around $31 million. It was founded by the Koch brothers and is committed to free markets and other libertarian causes.

These two groups do not often agree with each other, but when they do, it is worth taking note of what they are saying.

I was interviewing Rolf Skar, Special Projects Manager at Greenpeace who directs the organizations forestry campaigns. He told me something which sounded as though it could have come straight from the Cato Institute and, in particular, from Catos Nobel Prize-winning economist, Hernando de Soto.

Skar argued that one of the biggest problems, and biggest contributions to deforestation in Indonesia is lack of transparency around land ownership rights. Theres no single map defining land ownership, and the system has become hopelessly corrupted.

Any official with a Sharpie can change the map. This corruption allows small landowners to be bulldozed aside with no recourse to defending their rights in court. He suggested the situation was similar in Brazil, and, no doubt, in many other countries.

Poorly defined ownership rights create what economists call dead capital. This is something to which people have a de facto claim, but not one that is backed up in law. De Soto estimated in 2015 that around 5.3 billion people own almost $10 Trillion in dead capital.

Examples of dead capital include land where ownership records are unclear or contradictory, or where there is no legal recourse to enforce ownership rights.

Other examples include informal dwellings built on land that is not designated for residential building.

This happens in heavily regulated cities in developed countries but is far more widespread in the developing world. Market traders respect each others ownership of a particular roadside pitch or timeslot in lieu of a formal record of ownership.

Without official title, these owners cannot sell or bequeath their assets nor can they borrow money secured against their ownership. Theres no opportunity for their enterprises to grow fracturing the cascade of wealth between the generations.

Corruption and incompetence in administration is leading governments on every continent to fail in one of their foremost duties: protecting the rights of people to build better lives for their families.

Massive devastation of the worlds forests is just one of the consequences. Trapping people in poverty and the destruction of indigenous peoples follow from the same inability to protect land rights.

When such opposing organizations as Greenpeace and the Cato Institute are aligned on their analysis of the problem, there must be potential for cooperation: a manifesto or charter for land rights that both can endorse.

This, then, is the challenge: Can Greenpeace and the Cato Institute come together to negotiate such a manifesto? It would be a statement of the problem alongside an outline of steps which governments can take to solve the problems.

Any 21st century solution to the problem of poorly defined ownership rights is likely to be built on incorruptible, probably non-governmental platforms.

An unhackable blockchain property rights register can operate entirely outside the control of corruptible officials.

Since we are seeking a decentralized system, it makes sense to get it adopted in a few countries first. The early adopters will benefit from early investment and a smoother transition to a functioning economy, but later adopters may benefit from tweaks to the technology.

Indonesia is the fourth-largest country in the world by population and 14th by land area. Brazil is the sixth-largest by population and fifth by area, so these two should be enough to be going on with.

Corruption is an insidious cancer which corrodes cooperation and sews cynicism. It tilts power and wealth away from voluntary exchange towards force and coercion.

Rainforests are home to the trees which sequester carbon, the biodiversity which promises future pharmacological breakthroughs and previously undisturbed indigenous peoples. Corruption of land records threatens all of this.

For the first time, technology offers a solution to the problem that devastates the environment and blights the prospects of some 70% of the worlds people.

The practical experience and the moral weight of Greenpeace and Cato can map a path to the solution.

Read more:
Where Greenpeace and Cato Align - The Globalist

To understand the effects of circadian phase on mice behavior, 24 mice were divided into two groups when 4week-old (active phase: mice were maintained in reverse light; inactive phase: mice were maintained in normal light). All mice (8week-old) during the active and inactive phases were subjected to a battery of behavioral tests (initial test), including: rotarod, von Frey test, open field, elevated-O-maze, lightdark box, water maze, T-maze, contextual fear conditioning, and active avoidance. To further confirm the results at a different age, all the behaviors were repeated again three months later (retest, 20week-old) (Fig.1A). Behavioral testing was started two hours after lights on/off; Zeitgeber Time (ZT) 14 for the active group and Zeitgeber Time (ZT) 2 for the inactive group. Ten minutes before the test, tested cages were relocated from animal room to the waiting hallway (red dim light, 15lx) to minimize the effect of light (Fig.1B). Tests were then conducted under the following light intensities: open field (400lx), elevated-O-maze (350lx), lightdark box (440lx), water maze (440lx), T-maze (400lx), contextual fear conditioning (inside the dark box), and active avoidance (inside the dark box).

Effects of diurnal phase on motor coordination and sensory stimulation. (A) Time course of the experimental procedure. Two groups of mice (n=12; 6 males and 6 females in each group) were housed in normal light and reverse light condition. Behavioral tests were conduct 2h after lights on/off (ZT 2 for inactive group, and ZT 14 for active group). (B) The relative position of animal rooms (one reverse light, one normal light) and behavioral testing rooms of the animal house unit. (C) Illustration of rotarod test (left), there is no difference detected in the latency to fall between active group and inactive group in neither the initial test (middle), nor the retest 3months later (right). (D) For von Frey test, mice tested in the active phase exhibit a slightly more sensitive in cutaneoussensory testing than mice tested in the inactive phase in the initial tests. Three months later, mice tested in the active phase still exhibit more sensitivity to filament stimulus compared to mice tested in inactive phase. Blue circles: male mice; Red circles: female mice.

To test the influence of the lightdark cycle on motor coordination and sensory stimuli, mice were subjected to the rotarod and von Frey tests. Our results show that there are no differences on the latency to fall in the rotarod test between inactive and active groups in the initial test (p=0.54, t(22)=0.61), nor the retest three months later (p=0.94, t(22)=0.07) (Fig.1C). Next, to assess sensitivity to sensory stimuli, all mice were subjected to the von Frey test; a mechanicalstimulationbya filament to hind paws. Mice tested in the inactive phase are slightly less sensitive in the initial test (p=0.049, F(1,44)=4.06). For the retest three months later, the results are similar to the initial test, mice tested in inactive phase are still less sensitive than tested in active phase (p=0.0085, F(1,44)=7.59) (Fig.1D). These results suggest that the performance of motor coordination and balance is not influenced by diurnal activity, but cutaneoussensitivity is more responsive in the active phase.

To better understand the effects of diurnal rhythm on anxiety, we chose three common tests associated with anxiety like behavior: the open field test, elevated-O-maze, and lightdark box. All mice were subjected to these three tests. Our results show that there were no significant differences detected between inactive and active groups in the open field test in the initial test (travel distance, p=0.25, t(22)=1.17; time in center zone, p=0.09, t(22)=1.72), nor the retest three months later (travel distance, p=0.89, t(22)=0.13; time in center zone, p=0.57, t(22)=0.56) (Fig.2A). For the elevated-O-maze test, there were no significant difference detected in the initial test (travel distance, p=0.244, t(22)=1.19; during in the open arms, p=0.11, t(22)=1.64). However, mice tested in inactive period showed higher travel distance (p=0.01, t(22)=2.62) and exhibited a trend to stay longer in the open arms (p=0.06, t(22)=1.94) in the retest (Fig.2B). Next, we subjected all the mice to the lightdark box test, in the initial test there were no differences in time spent in the light compartment: p=0.75, t(22)=0.31). Three months later, all mice were subjected to the tests again. Mice tested in the inactive period spent more time in the light compartment (p=0.036, t(22)=2.23) (Fig.2C). The results show that there were no remarkable differences observed in anxiety tests while testing mice during active or inactive periods in the first test. However, three months later upon retesting, we did observe that mice exhibited less travel distance in the elevated-O-maze and spent less time in the light compartment.

Effects of diurnal phase on anxiety tests. (A) There is no significant difference in distance traveled or time spent in the center zone of open field between active and inactive groups in the initial test, nor in the retest 3months later. (B) In the elevated-O-maze, there is no significant difference detected in distance travel or times spent in the open arms between active and inactive groups. However, 3months later, the mice from the inactive group travelled a higher distance, but with no significant difference in time spent in the open arms in the retest. (C) In the lightdark box, there is no significant difference in time spent in the light box in the initial test. In the retest 3months later, mice tested in active phase spent less time in the light compartment. Blue circles: male mice; Red circles: female mice.

It is unclear whether a time-of-day may influence the performance of spatial learning and memory. To investigate the effects of diurnal rhythm on spatial learning and memory, the water maze was used. All mice were subjected to the water maze for 4 days to examine acquisition. The results show there were no differences in escape latency (p=0.24, F(1,22)=1.45) and travel distance (p=0.85, F(1,22)=0.03) in the initial test, nor the retest three months later (escape latency, p=0.53, F(1,22)=0.39; travel distance, p=0.65, F(1,22)=0.2) (Fig.3A). Seven days after the last training, the escape platform was removed, and mice were subjected to the water maze, and spatial memory was evaluated. There were no significant differences detected between the active group and inactive group for the initial test (time spent in target zone, p=0.82, t(22)=0.22; platform crosses, p=0.06, t(22)=1.9), nor the retest three months later (time spent in target zone, p=0.21, t(22)=1.28; platform crosses, p=0.22, t(22)=1.25) (Fig.3B). These data suggest that there are no obvious differences detected in spatial learning and memory between mice tested in active or inactive period.

Effects of diurnal phase on spatial learning and memory. (A) During water maze training, there is no difference in escape latency or travel distance between active and inactive groups, neither in the retest 3months later. (B) For the memory retrieval of the water maze, there is no significant difference detected in time in target zone or platform crosses 7days after the last training, nor in the retest. Blue circles: male mice; Red circles: female mice.

Next, to better assess whether the circadian period affects other types of cognitive behavior, we conducted T-maze, contextual fear, and active avoidance tests. For T-maze alternation, the results show there were no differences in percentage of correct choices in the initial test (p=0.79), nor the second test three months later (p=0.8) (Fig.4A). For contextual fear conditioning, there were no differences detected in freezing time during the pre-shock session (p=0.07, t(22)=1.88), and there was no difference in freezing time detected in the test session 24h after the shock (p=0.15, t(22)=1.47) (Fig.4B). Three months later, all mice were subjected to the footshock chamber again. Mice tested in the active phase exhibited an increase in freezing time during the pre-shock session (p=0.007, t(22)=2.94), but no differences during the test session (p=0.21, t(22)=1.27), suggesting mice tested in the active phase show better long-term memory of the footshock chamber (Fig.4B). For active avoidance, mice tested in the active period exhibited higher escape success rate than those tested in the inactive phase (p=0.0028, t(22)=3.36), suggesting that mice learn active avoidance better during the active phase. Three months later all the mice were subjected to active avoidance testing again, and the results show there was no significant difference (p=0.25, t(22)=1.15) (Fig.4C). Clock genes have been extensively studied and show circadian expression in the brain11,12. To further confirm physiological gene expression pattern of active and inactive periods in these mice, three days after the last behavioral test, we harvested hippocampal tissue for clock gene expression four hours after lights on/off. Our results show that hippocampal tissue harvested in the active period (Zeitgeber Time 16, ZT16) exhibit higher expression of Per1 (p=0.0001, t(8)=6.74) and Per2 (p=0.0013, t(9)=4.57), and lower expression of Bmal1 (p=0.0049, t(9)=3.69) compared to tissue harvested during the inactive phase (Zeitgeber Time 4, ZT4) (Fig.4D). These results confirm the mice had differential gene expression between active and inactive phase.

Effects of diurnal phase on T-maze, contextual fear, active avoidance, expression of clock genes. (A) In the T-maze test, there is no significant difference in the percentage of correct choices observed influenced by diurnal rhythm, nor in the retest. (B) For the contextual fear conditioning, there is no difference in freezing time during the pre-shock session between active and inactive groups. Twenty-four hours after the footshock, both active and inactive groups show increased freezing time during the test session, but no significant difference was detected. Three months later, mice tested in active phase exhibited a higher percentage of freezing in the pre-shock session, but no difference in freezing time during the test session. (C) For active avoidance, mice tested in the active phase feature higher escape success rates compared to mice tested in the inactive phase. In the retest, no significant difference is detected. (D) The phase differences in expression of clock genes (Per1, Per2, and Bmal1) in the hippocampus at ZT4 (inactive group) and ZT16 (active group). Blue circles: male mice; Red circles: female mice.

In order to determine whether differences in sex could be contributing to our results, for each measure we compared a model in which phase predicted the behavior to a model that in addition contained sex as a predictor. We applied a Bonferroni 5% corrected threshold of 0.00156 to take into account the fact that we ran 32 tests (0.05/32=0.00156). Our figures show results for males and females where males are colored blue and females colored red. We found two behavioral results exceeded the 5% threshold; time spent in open arms (p=0.00017) and travel distance (p=0.0012) of elevatedO-maze at 20weeks in our analysis. However, the small sample size and consequent low power means we cannot exclude the presence of a sex difference. Table 1 provides a summary of the sex difference analyses.

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Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice | Scientific Reports - Nature.com