NWBO: Once In A Decade Best Stock Investment -- Regulatory Approvals Coming! [Dec10, 2022 在第一页加了中文简述]

He (AF at Statnews) is at it again, another hit piece released this morning. For those who want to get in this ongoing incredible ride of nwbo to success today may present an opportunity to get in or otherwise the price would be much higher. Shorts will never rest as expected.

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Opportunities once again come presenting itself thanks to AF's hit piece. Aim at the big prize while shorts dig deeper, meaning much higher price in the future.

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Good for you investor2013. I also intended to buy some more yesterday but was a couple of cents short my target of about $0.93 so unfortunately no deal for me yesterday.

I have averaged up too, from as high as $1.60s all the way down to $0.30s to 0.40s. Now with too large a position, I have become more hesitate to add much more shares. One exception is if the share price drops substantially than my rule of not adding too man more will change.

Remembered last time on 10 May the price was dropped from around $1.5 to $0.30s with his hit piece with about 60 million trading volume, and this time the price dropped from $1.15 to as low as $0.95 but ended day at $0.99 with a much decreased volume of about 12 millions. So I think it's obvious the power of short cabal (AF's hit piece served as starting pistol) has been diminishing.

Now the ball in the court of long, waiting for news, actions, etc.
 
最后编辑:
For those who are interested in who our principal investigator Dr Linda Liau is. Below is her story.

Resiliency of a perpetual optimist: neurosurgeon Dr. Linda Liau

It is not possible to capture all the depth that composes Dr. Linda Liau: chair of the Neurosurgery Department at the University of California, Los Angeles; second woman to chair a neurosurgery program in the United States; first woman to chair the American Board of Neurological Surgery; first woman president of the Western Neurosurgical Society; and one of only a handful of neurosurgeons elected to the National Academy of Medicine. Her childhood and family history alone could fascinate several chapters of her life’s biography. Nonetheless, this brief biography hopes to capture the challenges, triumphs, cultural norms, and spirit that have shaped Dr. Liau’s experience as a successful leader, scientist, and neurosurgeon. This is a rare story. It describes the rise of not only an immigrant within neurosurgery—not unlike other giants in the field, Drs. Robert Spetzler, Jacques Marcos, Ossama Al-Mefty, and a handful of other contemporaries—but also another type of minority in neurosurgery: a woman.

Keywords: women in neurosurgery; neurosurgical leaders; biography; immigrant neurosurgeons; diversity
Even among the highly select group of people that compose the neurosurgical community, Dr. Linda M. Liau stands out as an incredible anomaly. To those with limited insight into neurosurgery, she is a walking contradiction: small in stature and introverted by nature. But look closer and she is also a leader among leaders in the field, who paved a path for herself that few have before. Equal parts intelligent and humble, she found an identity within the profession that is uniquely her own.

Now the chair of the Department of Neurosurgery at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), Dr. Liau is only the second woman, and the first Asian American woman, in the United States to chair an academic neurosurgical department (2017).1 To this day, in 2020, there have been only four female chairs of neurosurgery programs in the US. Dr. Liau has held many titles as the first woman: chair of the American Board of Neurological Surgery (ABNS) (2019–2020),2 president of the Western Neurosurgical Society (2015–2016), editor-in-chief of the Journal of Neuro-Oncology (2007–2017), elected member of The Society of Neurological Surgeons (2013)3 and the National Academy of Medicine (NAM) (2018),4,5 and countless other leadership and scientific accolades. She is a wild success by any standards.

Sitting across from Dr. Liau at a table, one sees her calmness and candor shining through, as well as her youthful glow; years of neurosurgery do not seem to have worn her down. There is a spark in her eye. She speaks in a reassuring, easy tone that one presumes her mother used even after a long day in the labor factories of downtown Los Angeles. This is Dr. Linda Liau’s story.

Part 1: Childhood
Dr. Liau’s mother, Sue Hong-Tsu Liau, came from a family of merchants. Sue’s mother (Linda’s grandmother) was born one of 9 girls into a wealthy Taiwanese family before the Chinese Communist revolution. Three of the girls were exchanged for an adopted brother, who acquired the family name and family inheritance. The women in the family inherited nothing; girls were viewed as a liability to be given as dowry to a future husband.

Customary for the time, at the age of 21 years, Linda’s mother was offered to her father, John Ta-Lang Liau, in an arranged marriage in the town of Tainan in southern Taiwan. Shortly after they were married, John emigrated to the US to attend graduate school at Case Western Reserve University. Sue, who spoke no English, traveled to the US to join John and, returning to Taiwan pregnant, gave birth to a daughter. Linda Liau was born in Tainan, Taiwan, in 1967 (Fig. 1).

FIG. 1.
FIG. 1.
Family photograph of Dr. Linda Liau, younger than 1 year of age, in Tainan, Taiwan, 1967, with her mother, Sue Hong-Tsu Liau. Copyright Linda Liau. Published with permission.

Although her father studied in the US prior to her birth, Linda grew up in a decidedly traditional Taiwanese household, deeply entrenched with many gender disparities. She muses that her father likely had always wanted a boy, though he ended up with two girls, Linda and her younger sister, Anna, now a lawyer, who was born in Springfield, Ohio, following her mother’s return to the US. Linda recalls little of her childhood in Ohio except for the sideways glances or gawks she and her family received at the neighborhood Kmart. Revisiting childhood photographs, she reflects that she seemed to be the only non-Caucasian in her preschool classes.

When Linda was 5 years old, her parents moved their young family to Magnolia Avenue by the present-day University of Southern California. The area was decidedly inner-city and poor. Her family continued to be a recognizable minority among primarily Black and Hispanic neighbors. She attended the still-standing 32nd Street Elementary School, a public school with few resources at the time. In the third grade, her parents were able to secure her a spot at St. Vincent’s School (a predominantly Hispanic, Catholic school in downtown Los Angeles)—despite not being Catholic—with hopes for better educational resources.

Her parents valued education and did their best to provide for their daughters during their humble beginnings. Her father worked toward a real estate license, and her mother worked long hours at the equivalent of various sweat shops in downtown Los Angeles. Her mother held many odd jobs, one as a seamstress, which became Dr. Liau’s first job as a child. She earned a few cents per article of clothing by stringing up laces on women’s garments that her mother had brought home to work on.

Her mother in particular supported Linda’s academic success. Sue had only completed high school and had not been given a chance to pursue higher education. Before she married, Sue’s fate in life was to tend the modest family stall at the swap meet in their small hometown in Tainan, selling knick-knacks and wrinkled plums. Meanwhile, Sue’s family’s resources had been allocated to her three brothers: one became a doctor, one inherited the family stall at the swap meet, and one became a schoolteacher. Sue always envied her physician brother; it was her dream to pursue a career in medicine. Instead, her brother lived out her dream. He attended medical school, residency in New York, and moved back to Taiwan as a head and neck surgeon. Sue wanted more for her daughters than had been available to her.

A gifted child in math and science, Linda would soon be able to chart her own course in life, even without the resources that her parents could not offer her. By the fifth grade she had intellectually outgrown the material taught in class. She was unexpectedly pulled from classes for 3 days for a barrage of psychological and IQ tests by the school guidance counselor. Shortly thereafter, she was placed directly into seventh grade at a new college-prep school that was recruiting gifted students, Whitney High School, on which the book School of Dreams: Making the Grade at a Top American High School (2003) is based. By this time, her mother had started working as a bank teller and her father had earned his real estate license. Though still struggling to make ends meet, they were now better able to support her junior and high school education in another city, so the family moved to Cerritos, California.

Linda’s early academic prowess and internal drive were evident, thereafter earning her acceptance to a variety of nationally prestigious academic programs. But, despite all her accomplishments to date, Dr. Liau states that her mother remains the smartest person she has ever known.

Part 2: Education
Her mother’s words of constant encouragement, and her dream of being a physician to help people, lingered in Linda’s mind when she moved 3000 miles away at the age of 16 years to Brown University’s 7-year medical education program. During her undergraduate years, she majored in biochemistry and political science. Still in need of monetary support for her education, she arrived at Brown on work study. She found a job in a laboratory cleaning glassware. Her relentless curiosity and intellectual drive soon got the best of her, and she could not help but inquire about the work the postdoctorates were doing in the laboratory. Not long after, the laboratory principal investigator (PI), Dr. Jean M. Marshall, began involving the inquisitive young Linda in a variety of laboratory projects. The research focused on gastrointestinal motility, but Linda was singularly fascinated by the role of the nervous system in this complex process. Dr. Marshall began to invest in Linda’s education and helped her complete her honors thesis in preparation for medical school. Although she could have stayed at Brown, Linda was tired of the weather and desperately homesick to return to California. Her laser focus on research drew her to the heavy-hitting academic neuroscience research centers. She graduated from Brown in 1987 and then attended Stanford University School of Medicine (1987–1991).

Upon arrival at Stanford, the budding scientist contacted a variety of neuroscience professors and heard back from neurology professor Dr. Stephen J. Peroutka. Linda’s technical laboratory skills blossomed, and, despite her PI leaving academia for a job in industry partway through her training, she had enough data to publish her first paper on the characterization of a novel serotonin (5-HT1A) antagonist, which was a pindolol derivative affectionately called “Lindalol” in the laboratory. She lightheartedly says she should have been studying serotonin agonists; it would have made her a fortune in a time before Prozac, which is now widely used for depression. But like most things in her life, she takes this in stride. One gets the sense that, despite her proclivity for goal setting and achieving, maybe she is driven most by the thrill of the intellectual journey.

Perhaps the only major setback in life that she felt wholly ill-equipped to deal with was the passing of her mother in 1994 after a 15-year struggle with breast cancer. With her mother’s worsening health and her PI having left Stanford, instead of completing her PhD through the National Institutes of Health (NIH)–funded Medical Scientist Training Program for the development of physician-scientists, she was convinced by her mother’s looming mortality that she needed to “get on with life” and find a way back to Los Angeles to care for her. Linda returned to clinical rotations her 3rd year of medical school. Carrying her deeply rooted interest in neuroscience through her rotations, she could not identify with the hands-off feel of neurology, and felt a slow personal descent after rotating on a locked psychiatric ward with severely affected patients. She rotated on neurosurgery last and found a perfect fit, her sense of wonder again peaked.

On this rotation, Linda met Dr. Frances Conley, the first woman to be granted a tenured professorship in neurosurgery at a US medical school (1982), and first to be a full professor of neurosurgery (1986). Dr. Conley was both physically and intellectually impressive as an avid runner and javelin thrower, and a female general and spinal neurosurgeon who operated alongside all-male colleagues. She was also an early pioneer of the concept of harnessing the immune system, specifically by introducing bacteria (i.e., Corynebacterium parvum) into a tumor cavity to induce an immune reaction to potentially treat glioblastoma (GBM), which was thought of as a hopeless death sentence at the time. This was a radical idea for the time, potentially inspiring some of the groundwork for Linda’s later research on brain tumor vaccines and immunotherapy.

Dr. Conley, along with attendings such as Drs. Gary Steinberg, Larry Schuer, and John Adler (inventor of the CyberKnife), supported Dr. Liau as she pursued her passion for neurosurgery while a medical student at Stanford. She sought out UCLA as a perfect fit for residency; it not only brought her back “home” to Los Angeles to be near her ailing mother but also was famous for research in traumatic brain injury under the leadership of Dr. Donald Becker. She saw an opportunity to start research in the field of identifying biomarkers and new treatments for head trauma and brain injury.

In 1991, she graduated from Stanford Medical School (Fig. 2) and started neurosurgery residency at UCLA (Fig. 3). Though physically closer to her mother, Dr. Liau now lacked time to devote to Sue’s care. Her sister, Anna, took their mother to doctor appointment after doctor appointment. The family struggled to get Sue into a clinical trial for Herceptin, which was not yet FDA approved. By the time Sue’s care was transferred to UCLA oncologists Drs. John Glaspy and Dennis Slamon (who developed Herceptin), her cancer had widely metastasized, including to her brain. When Dr. Liau’s mother passed during her 4th year of residency, she experienced the greatest regret and guilt of her life: that she had been unable to spend more time caring for her mother in those final days.

FIG. 2.
FIG. 2.
Dr. Linda Liau graduating from Stanford Medical School, 1991. Copyright Linda Liau. Published with permission.

FIG. 3.
FIG. 3.
UCLA neurosurgery residents, 1997. Dr. Linda Liau is pictured in the front row, second from right. Copyright UCLA Department of Neurosurgery. Published with permission.

Ever trying to make sense of the insensible, Dr. Liau drastically shifted her intellectual and research efforts toward oncology. The year her mother died, she entered the fledging UCLA Specialty Training and Advanced Research (STAR) Program, allowing her to pursue a PhD degree during residency/fellowship, which she completed in 1999. That same year, she received an NIH K08 grant under the mentorship of Dr. James Economou (her mother’s surgical oncologist), applying the principles of immunotherapy for melanomas and carcinomas to cancers of the brain, specifically GBMs. He would go on to be her academic mentor throughout her professional career as a faculty member at UCLA. When Dr. Liau was elected to NAM in 2018, Dr. Economou was at the awards ceremony beaming with pride.

Around the time when Dr. Liau started on faculty at UCLA, her previous mentor, Dr. Fran Conley, still at Stanford, experienced a great setback. Dr. Conley was professionally respected among her male peers, who dominated the specialty at the time. But, having been passed over for chairman positions, she authored Walking Out on the Boys (1998), chronicling her challenges as a woman in medicine. She lost favor in the neurosurgical community thereafter. But she was 30 years ahead of mainstream culture, and though she was a martyr for the cause of advancing women in medicine, she is now noted as a pivotal catalyst in history books. The professional fall of a prodigious mentor greatly saddened Dr. Liau, but she intended that she too would be a role model someday, if only she made it that far.

Part 3: Professional and Adult Life
Dr. Liau is potentially one of the few neurosurgical figures who is simultaneously endowed with all aspects of success. In addition to being a coveted physician-scientist, she is a successful leader, role model, wife, and mother. She is commonly asked how she balances everything, to which she refreshingly and unabashedly responds, “You don’t. You can’t balance it all synchronously, but you can have it all, in parts, at various stages of your life.”

Stage 1: Mother, Scientist
She explains that early in her faculty career, she embarked on her greatest accomplishments to date with the births of her two children, Brandon Bergsneider, born in 1998 (she operated until her water broke in the operating room), and Bianca Bergsneider, born in 2001 (Fig. 4). Her pregnant belly seemed to limit new patient recruitment, so she made the most of her time as a young attending developing her laboratory and research, while being a mother to two young children alongside a husband who was also a busy practicing neurosurgeon. She somehow managed to breastfeed and pump between cases for a year for each of her children; it was not easy. But she smiles as she mentions their names.

FIG. 4.
FIG. 4.
Family photograph (left to right): Dr. Marvin Bergsneider, Bianca Bergsneider, Dr. Linda Liau, and Brandon Bergsneider at the Rose Bowl, June 2019. Copyright Linda Liau. Published with permission.

With funding from her initial NIH K08 award, she hired Dr. Robert Prins, who had just completed his PhD at the Medical College of Virginia, as her first postdoc, and Sylvia Odesa as her laboratory manager. Dr. Liau seems to be deeply loyal; Dr. Prins now has his own laboratory and is a full professor in the Department of Neurosurgery at UCLA, and Ms. Odesa remains her laboratory manager to this day. In this early phase of her career, Dr. Liau made the seminal discovery that cytotoxic T cells can be activated in vivo to traffic into brain tumors, despite the long-held dogma at the time that the brain was “immune-privileged” and devoid of immune reactivity.6 By the time she was a 5th-year faculty member, she had already completed the first-in-human treatment of a GBM patient with a dendritic cell (DC) vaccine (1999) and started the first-in-human phase I/II trials of an autologous tumor lysate-pulsed DC vaccine (2003).7 She had identified a novel glioma-associated growth factor gene8 and developed a new Listeria vaccine in animal tumor models.9 By the time she was 34 years old, she had earned three NIH R01 grants and an R21, a seemingly impossible academic feat in such a short period of time. As she would say, “the numbers speak for themselves,” and indeed others seemed to agree.

At one of her many national plenary talks about her research, she was approached by the American Association of Neurological Surgeons/Congress of Neurological Surgeons Tumor Joint Section president at that time, Dr. Joseph Piepmeier, and asked if she would be interested in joining the Tumor Section’s Executive Committee. Dr. Piepmeier became a mentor to Dr. Liau, and she later succeeded him as the editor-in-chief of the Journal of Neuro-Oncology. As she continued to develop her research acumen, she discovered a relationship between cytomegalovirus viral immunity and tumor immunity in GBM patients10 and was involved in the landmark discovery that cancer-associated IDH1 mutations produce 2-hydroxyglutarate.11 Because of her groundbreaking research, her notoriety on the national stage grew and leadership opportunities started flooding in, whether for department chair, national board positions (Fig. 5), journal editorships, or standardizing policies regarding neurosurgical practice.

FIG. 5.
FIG. 5.
ABNS 75th Anniversary and Mary Louise Spencer’s (executive administrator for the ABNS for almost 30 years; middle of first row, gray dress) retirement party, June 27, 2015. All of the other people in the photograph were current or former ABNS board directors. Dr. Linda Liau is pictured in the front row, third from right. Copyright American Board of Neurological Surgery. Published with permission.

Stage 2: Clinician, Leader
Having developed a strong basic/translational science foundation, Dr. Liau transitioned into the next stage of her career—a focus on patient care built upon a reverence for life, as she daily encountered GBM patients who had abandoned all hope. There are patients from her early immunotherapy vaccine trials who are now surpassing all odds, living up to 17 years after their deadly diagnosis was made, with phase III trials derived from her initial preclinical discoveries and phase I clinical results currently still ongoing. While she grew her clinical practice, her notoriety allowed her to grow an extended professional network within neurosurgery as well.

She speaks of her patients and neurosurgery colleagues fondly, as if they are extended family. In weaving together the narrative of her life, one starts to understand that she is the kind of person whose talent begets talent, whose relentless curiosity and perhaps joyful obsessiveness with her research engender infectious creativity and thoughtfulness in others.

Stage 3: Role Model, Historical Figure
Three years ago, Dr. Liau transitioned into her third professional stage of life as she took on the role of chair of the Department of Neurosurgery at UCLA (Fig. 6). She also transitioned into a symbol of inspiration nationally. She had accomplished firsts. She had become one for the history books. Her primary goals shifted from singularly personal research or clinical goals to facilitating the goals of others; shaping residents for their future, enabling other attendings to achieve their goals; and building the department she served.

FIG. 6.
FIG. 6.
Dr. Linda Liau (foreground) as chair of the UCLA Department of Neurosurgery (resident and faculty members in the background) on Department Photo Day, July 2017. Copyright UCLA Department of Neurosurgery. Published with permission.

Deeply humble, she plays off her countless research, clinical, and leadership triumphs as mere kismet, but this volume of achievement cannot be accomplished without sheer grit and determination. Despite being a staunch intellectual, strongly swayed by numbers and statistics, it is clear that she is a deeply optimistic, hopeful individual. She has to be, in order to muster such resiliency for herself and for her patients. Her delightful wonder about the world is reflected in the glimmer in her eyes as she talks about all that she still hopes to accomplish in her already wildly successful career.

Part 4: Parting Wisdom
To merely chronicle the experiences of Dr. Liau’s life, the facts and the figures that make her curriculum vitae exceptional, is to overlook the extraordinary human being. Her humility, grace, and empathy, perhaps sometimes to a fault, often prevent those on the outside from truly understanding the daily challenges she must have faced. She was an immigrant and racial minority for most of her childhood, then rose as a star in a profession historically dominated by men.

Though she speaks little of it, one can infer the lifetime of explicit and implicit challenges she has faced, whether because of her race or her gender. Her extreme resilience, whether natural or developed as a coping mechanism to persevere, typifies who she is at her very core. Her sense of self is strong; it had to be to get this far in life and to live up to her strongest female role model, her mother. She is so deeply empathetic that she interprets slights and prejudices against her as a woman in the field as reflective of insecurities or ignorance of the offender. In such cases, Dr. Liau expands pattern recognition and demonstrates that women can excel in the profession. It is with singular insight that one can begin to see how—now in her seat of power, still likely subject to some nonbelievers—she is able to shrug off all that she has endured.

At the top of her field, Dr. Liau serves as a de facto mentor for young women in neurosurgery everywhere (Fig. 7). She always recommends that women medical students interested in neurosurgery talk to current residents; neurosurgery residency has significantly changed in the last 20 years, she says, perhaps with both a wistful and decidedly “as it should be” tone. I sometimes wonder how many volumes her challenging experiences could fill. I wonder how she endured both emotionally and intellectually. But I know she does not give it a second thought. She simply refuses to let the world dictate her life, perhaps as a reflection of her favorite quote:
No one can make you feel inferior without your consent.

— Eleanor Roosevelt

FIG. 7.
FIG. 7.
Dr. Linda Liau and her first female trainees as department chair. A: Dr. Linda Liau (left) and Dr. Jos’lyn Woodard (right), fellow (2020 graduate). B: Dr. Jasmine Thum, post graduate year (PGY)–5. C: Dr. Sophie Peeters, PGY-4. D: Dr. Maya Harary, PGY-2. Copyright Sophie Peeters. Published with permission.

And so she doesn’t.

Acknowledgments
I would like to thank Dr. Linda Liau for generously sharing her experiences with me for this piece, and for graciously sharing her advice and wisdom with me throughout the years.

Disclosures
The author reports no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

References
1?Mazziotta J, Martin KC, Spisso J. New Chair–Dr. Linda Liau. August 21, 2017. UCLA Health. Accessed January 20, 2021. Linda M. Liau, MD, PhD, MBA | Brain and Tumor Neurosurgery - Los Angeles, CA
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2?Schmidt E. Neurosurgeon-Scientist Takes Helm of UCLA Neurosurgery. September 26, 2017. UCLA Newsroom. Accessed January 20, 2021. Neurosurgeon-scientist takes helm of UCLA Neurosurgery
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3?Society of Neurological Surgeons. Dr. Linda Liau. Accessed January 20, 2021. Officers Detail - societyns.org
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4?Schmidt E. UCLA Neurosurgeon Named to National Academy of Medicine. UCLA Newsroom. October 15, 2018. Accessed January 20, 2021. UCLA neurosurgeon named to National Academy of Medicine
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5?UCLA Neurosurgeon Named to National Academy of Medicine. Professional Woman’s Magazine. Accessed January 20, 2021. UCLA neurosurgeon named to National Academy of Medicine│Professional WOMAN's Magazine
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6?Liau LM, Black KL, Prins RM, et al. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg. 1999;90(6):1115–1124.
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7?Liau LM, Prins RM, Kiertscher SM, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005;11(15):5515–5525.
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8?Liau LM, Lallone RL, Seitz RS, et al. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res. 2000;60(5):1353–1360.
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9?Liau LM, Jensen ER, Kremen TJ, et al. Tumor immunity within the central nervous system stimulated by recombinant Listeria monocytogenes vaccination. Cancer Res. 2002;62(8):2287–2293.
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10?Prins RM, Cloughesy TF, Liau LM. Cytomegalovirus immunity after vaccination with autologous glioblastoma lysate. N Engl J Med. 2008;359(5):539–541.
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11?Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739–744.
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Article has an altmetric score of 132
Contributor Notes
Correspondence Jasmine A. Thum: University of California, Los Angeles, CA. jthum@mednet.ucla.edu.
INCLUDE WHEN CITING DOI: 10.3171/2020.12.FOCUS20954.

Disclosures The author reports no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Keywords: women in neurosurgery; neurosurgical leaders; biography; immigrant neurosurgeons; diversity
 
Added another 30k shares today. Both yesterday and today, I used money not supposed for any purchases. My another crazy average up. :-(
 
Good to hear you added more. The short are taking the bet that there will be some time before the company can get its DCVax-L (Murcidencel) approved, first BLAs have not yet file, then the acceptence, the PDUFA day. So that's it. But the company can still pull in a lot of positive news like commercial manufacturing license for UK and EU, partnerships, etc, most importantly a huge awareness of the general market about this company and its promising future.

Or just even the onboard of one single big fish (big name or big institution) will completely crash the short.

Btw, below is a Seeking Alpha analysis which in general is level headed, a good summary but still errors laden on some not significant issue:

Northwest Bio: Data Is Done, Just Wait For Approval (OTCMKTS:NWBO)

Northwest Biotherapeutics: Data Is Done, Just Wait For Approval​

Nov. 23, 2022 7:20 AM ETNorthwest Biotherapeutics, Inc. (NWBO)7 Comments

Summary​

  • NWBO published topline data on JAMA Oncology, resoundingly, I must say.
  • Data shows stat sig on all major primary and secondary endpoints.
  • DCVax-L is a winner, and so may NWBO be, soon.
  • Looking for more investing ideas like this one? Get them exclusively at The Total Pharma Tracker. Learn More »

Wall street sign in New York with New York Stock Exchange background



naphtalina/iStock via Getty Images


Last month, I was complaining about Northwest Bio (OTCQB:NWBO) not releasing data in a proper manner, which made it a confusing investment and a Hold for me. The company now is finally out with the topline data, published on November 17 on the peer-reviewed and well-regarded JAMA Oncology - here. The stock is up 70% and counting, one patient survived 8 years following DCVax-L treatment, a British patient survived 7 years, everything looks good, and all’s well with the world.

However, there’s talk about how the peer-reviewed article missed a few key points - the FDA’s partial clinical hold, the crossover design and the change in the endpoint - and how these things will make life difficult for NWBO. Well, they may or may not do so, but what these arguments miss is that I have never come across a peer-reviewed original investigation report that discusses anything but data and results. These other things are in the realm of the retail investing public - bears and bulls - and it is not the job of JAMA to figure that out. They only discuss data.

And the data was outstanding. Another thing I have hardly ever seen is a JAMA article with 67 named authors. Ms. Linda Powers has given this publication all she had, knowing full well that if there’s something that should shut the critics up for good, it would be from a publication like this with named authors who read like the who's who in glioblastoma expertise. [see appendix below for list of authors/affiliations.]



I wanted to put that out in order to show you that the scientific community seems to have given this all they could and have come together to support Dr Linda Liau’s discovery of DCVax-L.

Now let's review the data. Here it is, short and sweet and to the point:

A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (MOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03).

The active treatment here was DCVax-L plus standard of care temozolomide, which was approved nearly two decades ago. External control nGBM (newly diagnosed GBM) patients received temozolomide and placebo; while rGBM patients received “approved GBM therapies,” where there is no SOC. Results were statistically significant. I note that almost every endpoint measured except the methylated MGMT one achieved statistical significance. As the authors also note, “only 1 phase 3 trial in nGBM and no phase 3 trials in rGBM have demonstrated a survival benefit” since 2005. This successful phase 3 trial was with TTFields, a promising new therapeutic modality, plus temo. While PFS was the primary endpoint, OS was a secondary endpoint and the data was as follows:

Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone.

Note that for the nGBM population, DCVax-L also demonstrated 19.3 months of OS versus 20.9 months for the TTFields trial, however placebo had a 0.5 months higher survival in DCVax-L; of course, these cross trial comparisons do not really work. What should be noted is that both new therapies worked in nGBM; and DCVax-L also worked in rGBM patients, where nothing else works.

In the US, more than 13,000 people will be diagnosed with GBM in 2022 according to the National Brain Tumor Society. In the EU, there should be an equal number of patients; the UK alone has 2500 patients. Indeed, the EU number is actually quite a bit higher, at 22000 patients, according to this source. GBM occurs more in the developed countries than in the rest of the world; while this could be caused by underreporting, as one understands, the market is truly in the developed countries. There are some 1771 Japanese patients. From China, I had PBT (primary brain tumor) mortality data, which stood at 21,215. Assuming a 70% mortality and a 50% GBM among these PBT patients, I get a figure of 15,000 Chinese patients with GBM; which sounds a bit low given the population, and may or may not be caused by underreporting. Thus, there could be as many as 50,000-60,000 patients in the developed/relatively developed world for GBM. This is the target population for DCVax-L. Median treatment cost for GBM patients could well cross $100,000, and I wouldn’t be surprised if it goes beyond $200,000 per year. A treatment that extends OS significantly can be priced in the ballpark range - probably higher given how some very well-known people have succumbed to GBM. What that means is that a lot of people who could afford treatment did not survive due to a lack of it, so that could inform pricing. If we put it - quite randomly - at $200,000, then the total addressable market in the developed world comes to $12bn. TTFields treatment was approved for GBM patients by the FDA.

Coming back to the JAMA-Onc report, here’s something interesting - and to me, definitive- that it says about the crossover design:

Many trials, especially for incurable diseases, incorporate a crossover design for feasibility and/or ethical reasons. A crossover was considered necessary when our study began in 2007 to make patient enrollment and retention feasible when novel immunotherapies were not yet generally viewed as promising for cancer. The crossover was also important to justify the placebo group for patients undergoing a leukapheresis—an invasive procedure necessary for blinding and for manufacturing vaccine but offering no benefit to patients in the placebo group if they could not receive their autologous vaccine.

I think we can put that issue to rest.

Another issue that had vexed investors was pseudo-progression. The company explained why a change from a PFS endpoint to OS was necessary in order to avoid pseudo-progression:

The PFS end point became infeasible for this trial due to the challenges now well recognized in trying to distinguish true progression from pseudo-progression (including vaccine-induced immune cell infiltration).13 There were 494 imaging time points when possible progression was observed by the independent radiologists, and 256 of these (>50%) required adjudication due to discordant interpretations. Based on these assessments, the median PFS was 6.2 (95% CI, 5.7-7.4) months for patients receiving DCVax-L and 7.6 (95% CI, 5.6-10.9) months for the placebo group. This difference was not statistically significant (P = .47).

I have no particular comment here; I discussed pseudo-progression in another article.

A few other points to note:

  1. DCVax-L did particularly well with patients with poor prognosis, like older patients, or those with substantial residual tumors, rGBM patients and so on, compared to ECP (external control population).
  2. DCVax-L was well-tolerated. Of 2151 total doses of DCVax-L administered, only 5 serious adverse events were deemed at least possibly related to the investigational treatment. There were no immune rejection issues with the treatment.
  3. DCVax-L could work well with other treatment modalities like checkpoint inhibitors for example.

About the trial, Linda Powers, CEO of NWBO, said:

We are excited to see the meaningful survival extensions in glioblastoma patients treated with DCVax-L in this trial – particularly in the long tail of the survival curve, where we see more than double the survival rates as with existing standard of care. With well over 400 clinical trials for glioblastoma having failed over the last 15 years, it is gratifying to be able to offer new hope to patients who face this devastating disease.

Here’s some commentary from a Guardian article.

Financials​


NWBO has a market cap of $1.2bn and a cash balance of just $11.7mn (current assets). Now that they published TLD, they will have triggered a $15mn loan facility. Plus, like I said before, Ms. Powers, the CEO, had offered a loan to the company before when it was in a much weaker position than now; I am guessing she can do so again, now that it is looking stronger. Last quarter, the company spent $7.8mn in R&D and $8mn in G&A - here. If they continue at that rate, there's no cash; however, with the solid data that they have, they may be able to get cash, even through a market offering.

Risks​


NWBO's primary risks are two - lack of cash, and lack of clarity. I just discussed the cash problem. As for clarity, my previous coverages have touched on that. Like I grumbled in October:

If the company behaved like a normal company, announced official data, published, filed for approval - sued its detractors

It has published data now, so there's a lot more clarity. The company now needs to sit down with analysts and be willing to take questions and so on - like it used to do earlier. They went into a dormant phase in the long years while their trial was running. Now that they have TLD, they need to come out of that phase and get vocal again.

Bottomline​


NWBO went up over $2 in May when the company reported primary data at the New York Academy of Sciences. Now that they have their TLD in JAMA, the stock is just up to $1.15. This will be followed by an NDA, then PDUFA. Like all things NWBO, don’t expect a quick turnaround. However, things will start to move positively from here. Just a day before the publication, Sentinus, LLC took a large position in NWBO. Institutional interest is still quite low, at just .2%. I expect that to change as the company gains legitimacy. This would be a good time to buy the stock.

Appendix​


Here’s the full list of authors:

Linda M. Liau, MD, PhD1; Keyoumars Ashkan, MD, FRCP, FRCS2; Steven Brem, MD3; Jian L. Campian, MD, PhD4; John E. Trusheim, MD5; Fabio M. Iwamoto, MD6,7; David D. Tran, MD, PhD8; George Ansstas, MD9; Charles S. Cobbs, MD10; Jason A. Heth, MD11; Michael E. Salacz, MD12; Stacy D’Andre, MD13; Robert D. Aiken, MD14; Yaron A. Moshel, MD, PhD14; Joo Y. Nam, MD15; Clement P. Pillainayagam, MD16; Stephanie A. Wagner, MD17; Kevin A. Walter, MD18; Rekha Chaudary, MD19; Samuel A. Goldlust, MD20; Ian Y. Lee, MD21; Daniela A. Bota, MD, PhD22; Heinrich Elinzano, MD23; Jai Grewal, MD24; Kevin Lillehei, MD25; Tom Mikkelsen, MD, FRCPC21; Tobias Walbert, MD21; Steven Abram, MD26; Andrew J. Brenner, MD, PhD27; Matthew G. Ewend, MD28; Simon Khagi, MD29; Darren S. Lovick, MD30; Jana Portnow, MD31; Lyndon Kim, MD32; William G. Loudon, MD33; Nina L. Martinez, MD34; Reid C. Thompson, MD35; David E. Avigan, MD36;Karen L. Fink, MD, PhD37; Francois J. Geoffroy, MD38; Pierre Giglio, MD39; Oleg Gligich, MD40; Dietmar Krex, MD41; Scott M. Lindhorst, MD42; Jose Lutzky, MD43; Hans-Jörg Meisel, MD, PhD44; Minou Nadji-Ohl, MD45; Lhagva Sanchin, MD44; Andrew Sloan, MD46; Lynne P. Taylor, MD47; Julian K. Wu, MD47; Erin M. Dunbar, MD48; Arnold B. Etame, MD, PhD49; Santosh Kesari, MD, PhD50; David Mathieu, MD51; David E. Piccioni, MD, PhD52; David S. Baskin, MD53; Michel Lacroix, MD54; Sven-Axel May, MD55; Pamela Z. New, MD56; Timothy J. Pluard, MD57; Steven A. Toms, MD58; Victor Tse, MD59; Scott Peak, MD59; John L. Villano, MD, PhD60; James D. Battiste, MD, PhD61; Paul J. Mulholland, MD62; Michael L. Pearlman, MD63; Kevin Petrecca, MD, PhD64; Michael Schulder, MD65; Robert M. Prins, PhD66; Alton L. Boynton, PhD67; Marnix L. Bosch, PhD67

And here are their affiliations:

  • 1Department of Neurosurgery, University of California, Los Angeles
  • 2King’s College Hospital, London, United Kingdom
  • 3Department of Neurosurgery, Penn Brain Tumor Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 4Division of Neurology, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 5Givens Brain Tumor Center, Abbott Northwestern Hospital, Minneapolis, Minnesota
  • 6Columbia University Irving Medical Center, New York, New York
  • 7New York-Presbyterian Hospital, New York, New York
  • 8Preston A. Wells, Jr. Center for Brain Tumor Therapy, Division of Neuro-Oncology, Lillian S. Wells Department of Neurosurgery, University of Florida College of Medicine, Gainesville
  • 9Department of Neurological Surgery, Washington University School of Medicine in St Louis, St Louis, Missouri
  • 10Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Medical Center, Seattle, Washington
  • 11Taubman Medical Center, University of Michigan, Ann Arbor
  • 12Neuro-Oncology Program, Rutgers Cancer Institute of New Jersey, New Brunswick
  • 13Sutter Health, Sacramento, California
  • 14Glasser Brain Tumor Center, Atlantic Healthcare, Summit, New Jersey
  • 15Department of Neurological Sciences, Rush Medical College, Chicago, Illinois
  • 16Department of Neurology, The Ohio State University, Columbus
  • 17The Cancer Center of Columbus Regional Health, Columbus, Indiana
  • 18University of Rochester, Rochester, New York
  • 19University of Cincinnati, Cincinnati, Ohio
  • 20John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey
  • 21Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan
  • 22Department of Neurology and Chao Family Comprehensive Cancer Center, University of California, Irvine
  • 23Rhode Island Hospital, Providence
  • 24Long Island Brain Tumor Center at NSPC, Lake Success, New York
  • 25Department of Neurosurgery, University of Colorado Health Sciences Center, Boulder
  • 26Ascension St Thomas Brain and Spine Tumor Center, Howell Allen Clinic, Nashville, Tennessee
  • 27Mays Cancer Center at UT Health San Antonio, San Antonio, Texas
  • 28Department of Neurosurgery, UNC School of Medicine and UNC Health, Chapel Hill, North Carolina
  • 29The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
  • 30Advent Health, Kansas City, Kansas
  • 31Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, California
  • 32Division of Neuro-Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
  • 33Saint Joseph’s Hospital, Orange, California
  • 34Jefferson Hospital for Neurosciences, Jefferson University, Philadelphia, Pennsylvania
  • 35Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
  • 36Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, Massachusetts
  • 37Baylor Scott & White Neuro-Oncology Associates, Dallas, Texas
  • 38Illinois Cancer Care, Galesburg, Peoria
  • 39Medical University of South Carolina Neurosciences, Charleston
  • 40Mount Sinai Medical Center, Miami Beach, Florida
  • 41Uniklinikum Dresden, Dresden, Germany
  • 42Hollings Cancer Center, Medical University of South Carolina, Charleston
  • 43Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida
  • 44BG Klinikum Bergmannstrost, Halle, Germany
  • 45Neurochirurgie Katharinenhospital, Klinikum der Landeshauptstadt Stuttgart, Stuttgart, Germany
  • 46Seidman Cancer Center, University Hospitals–Cleveland Medical Center, Cleveland, Ohio
  • 47Department of Neurosurgery, Tufts Medical Center, Boston, Massachusetts
  • 48Piedmont Physicians Neuro-Oncology, Piedmont Brain Tumor Center, Atlanta, Georgia
  • 49Department of Neuro-Oncology, Moffitt Cancer Center
  • 50Pacific Neurosciences Institute and Saint John’s Cancer Institute, Santa Monica, California
  • 51Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada
  • 52UC San Diego Moore’s Cancer Center, La Jolla, California
  • 53Department of Neurosurgery, Houston Methodist Hospital, Houston, Texas
  • 54Geisinger Neuroscience Institute, Danville, Pennsylvania
  • 55Klinik für Neurochirurgie, Chemnitz, Germany
  • 56Baptist Health System, San Antonio, Texas
  • 57Saint Luke’s Cancer Institute, Kansas City, Missouri
  • 58Departments of Neurosurgery and Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island
  • 59Kaiser Permanente, Redwood City, California
  • 60University of Kentucky Markey Cancer Center, Department of Medicine, Neurosurgery, and Neurology, University of Kentucky, Lexington
  • 61Oklahoma University Health Science Center, Oklahoma City
  • 62University College London Hospitals, London, United Kingdom
  • 63Blue Sky Neurology/Neuro-Oncology, Englewood, California
  • 64Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada
  • 65Department of Neurosurgery, Zucker School of Medicine at Hofstra/Northwell, Uniondale, New York
  • 66University of California, Los Angeles
  • 67Northwest Biotherapeutics, Inc, Bethesda, Maryland

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fredpitts
Today, 8:34 AM
Comments (45)
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The company finally admitted they conducted an IA in 2015 when the trial was halted. It certainly wasn't halted for efficacy. They received a futility recommendation but since the product is safe, they were allowed to continue with patients already in the pipeline and not recruit any new patients.

This futility rec obviously forced them to change the primary endpoint.

"The overall one-sided type I error for the study was set at 2.5%. One of the two planned interim efficacy analysis was conducted in March 2015 after 56.4% of subjects had completed 6 months follow up. "

Dr. Liau has known about pseudoprogression since 2016 or earlier. She has spoken about it. Why wait until well after the release of blended data in 2018 to change the endpoints? Post hoc dredging is why.

Dr. Liau has also stated the importance of patient level data for control comparison. The external control arm has NO patient level data.

The company also indicated in their 10Q they can not move forward with regulatory approval until Advent completes it's statement of work #6 which was pushed into late 2023.

"the Company amended the SOW6 (the “Amended SOW6”) to (1) extend the service period through September 30, 2023, and (2) clarify the assessment and application of the milestones, and (3) add a sixth workstream ( The potential cost for all unearned stock awards for milestones not yet achieved was re-measured on the modification date and will be further re-measured until the date the milestone award is achieved and the stock awards are earned. If all of the 10 milestones are achieved (i.e., for all 6 workstreams that are prerequisites for an application for product approval, "

All these reasons are exactly why the latest article was nothing more than a P&D, as shown by the share price runup and volume followed by identical dumping.

longnwbo profile picture

longnwbo
Today, 8:27 AM
Comments (1.67K)
|
Thank you for again up-dating what is current with DCVAX L. The results are fantastic considering all the failed trials over 20 some years. I also wish the company would begin a "dog and pony" show to bring these results to the investment community. Also, thank you Mr. Smith for your continued research on NWBOi. It amazes me how manipulated the stock price is and is behaving. I do wish the company would fight back and I will text David Innes and ask him to. I hope other shareholders would also flood him with requests that lead to action.
 
The epic David vs Goliath fight (小人物赢大人物) is on the way, and maybe in its final stage.
 
This is the comments on DCVax-L results published on JAMA made by Chief Scientist, Caner Immunology at AstraZeneca. AstraZeneca could be one of big pharms which are interested in partner or buyout deal with NWBO:
1669232080210.png
 
最后编辑:
There is reason for the company to keep quiet despite blatant short assaults. Stock trading at this price is a buy on a short term horizon, a strong buy on a media to long-term horizon. My unit of calculation is not year but month.

1669385020015.png
 
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